ChemicalBook CAS DataBase List ethyl(4aS,9bR)-6-bromo-1,3,4,4a,5,9b-hexahydro-2H-pyrido[4,3-b]indole-2-carboxylate

ethyl(4aS,9bR)-6-bromo-1,3,4,4a,5,9b-hexahydro-2H-pyrido[4,3-b]indole-2-carboxylate synthesis

7synthesis methods

Product Name:ethyl(4aS,9bR)-6-bromo-1,3,4,4a,5,9b-hexahydro-2H-pyrido[4,3-b]indole-2-carboxylate
CAS Number:1059630-08-8
Molecular formula:C14H17BrN2O2
Molecular Weight:325.2

(4aS,9bR)-6-bromo-1H,2H,3H,4H,4aH,5H,9bH-pyrido[4,3-b]indole

1059630-13-5

541-41-3

ethyl(4aS,9bR)-6-bromo-1,3,4,4a,5,9b-hexahydro-2H-pyrido[4,3-b]indole-2-carboxylate

1059630-08-8

Example 3: Preparation of ethyl (4aS,9bR)-6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate Step 1: (4aS,9bR)-6-bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole (36.0 g, 0.142 mol) was dissolved in 50% aqueous sodium hydroxide to free the base, followed by extraction of the product with methyl tert-butyl ether (MTBE). Step 2: The above free base (36.0g, 0.142mol) was dissolved in THF (300mL), triethylamine (24mL) was added and cooled in an ice water bath. Ethyl chloroformate (13.5mL, 0.142mol) was slowly added dropwise over 1 hour using a syringe pump. After removing the ice water bath, the reaction mixture was continued to be stirred at room temperature for 1 hour. Upon completion of the reaction, it was filtered through a diatomaceous earth pad and the solvent was evaporated to afford ethyl (4aS,9bR)-6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate. 1H NMR (CDCl3, 300MHz): δ 1.20-1.35 (m, 3H), 1.73-1.85 (m, 1H), 1.85-1.99 (m, 1H), 3.22-3.52 (m, 3H), 3.52-3.66 (m, 1H), 3.66-3.95 (br, 1H), 3.95-4.21 (m, 4H), 6.60 (m, 4H). 4H), 6.60 (t, J = 7.7 Hz, 1H), 7.04 (d, J = 7.2 Hz, 1H), 7.20 (d, J = 8.1 Hz, 1H). Alternative method: the (S)-mandelate of (4aS,9bR)-6-bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole was used as starting material. To a 100 mL round bottom flask was added (S)-mandelate feedstock (5 g, 12.35 mmol), Na2CO3 (2.88 g, 27.17 mmol) and THF (25 mL). A solution of ethyl chloroformate (1.64 g, 15.11 mmol) in THF (5 mL) was added dropwise over 25 min at 25 °C. After the reaction mixture was stirred at 25 °C for 10 min, detection by HPLC showed less than 2% of starting material remaining and a product yield of about 98%. EtOH (12.5 mL) was added and about 30 mL of solvent (mostly THF) was removed by concentration under reduced pressure. H2O (37.5 mL) was added and the mixture was pH > 9. After stirring at room temperature for 1 hr, the product was filtered, the solid was washed with H2O (25 mL) and dried under vacuum at 58 °C for 16 hr to give a yellow solid of 3.9442 g (98% yield).1H NMR was consistent with the target product, and (S)-mandelic acid was not detected. hplc analysis showed a purity of the product of > 99%. lc-ms showed molecular ion peak M/e = 326 (M + 1).

1059630-13-5
59 suppliers
$45.00/50mg

541-41-3
0 suppliers
$21.00/5g

1059630-08-8
59 suppliers
$38.00/100mg

Yield:1059630-08-8 98%

Reaction Conditions:

with sodium carbonate in tetrahydrofuran at 25; for 1.33333 h;Product distribution / selectivity;

Steps:

3

Example 3: Production of (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro-lH- pyrido[4,3-b]indoIe-2(9bH)-carboxylate; (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro- 1 H-pyrido[4,3-b]indole-2(9bH)-carboxylate may be prepared by first optaining [4aS, 9bR]-6-bromo- 2,3,4,4a,5,9b-hexahydro-lH-pyrido[4,3-Z>]indole (36.0 g, 0.142mol)) as a free base by using 50% aqueous sodium hydroxide solution and extracting the product into MTBE. The conversion to (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro-lη-pyrido[4,3- b]indole-2(9bH)-carboxylate may then be done by cooling a suspension of compounds of [4aS, 9bR]-6-bromo-2,3,4,4a,5,9b-hexahydro-lH-pyrido[4,3-*]indole (36.0 g, 0.142mol)) in THF (300 ml) and triethylamine (24 ml) in an ice- water bath. Ethyl chloroformate is added dropwise (13.5 ml, 0.142mol) via a syringe pump over 1 hour. The ice-water bath is removed and the reaction mixture is stirred at room temperature for another hour. The reaction mixture is passed through a pad of celite and the solvent is evaporated to give (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro-lH-pyrido[4,3- b]indole-2(9bH)-carboxylate). ¹H NMR (CDCl₃, 300 MHz): 1.20-1.35 (m,3H), 1.73- 1.85 (m, IH), 1.85-1.99 (m, IH), 3.22-3.52 (m, 3H), 3.52-3.66 (m, IH), 3.66-3.95 (Br, IH), 3.95-4.21 (m, 4H), 6.60 (t, J = 7.7 Hz, IH), 7.04 (d, J = 7.2 Hz, IH), 7.20 (d, J = 8.1 Hz, IH).[0084] Alternative to the use of [4aS, 9bR]-6-bromo-2,3,4,4a,5,9b-hexahydro- lH-pyrido[4,3-Z>]indole (Compound of Formual 1C) free base, the reaction may also be done by starting with the (S)-mandelate salt of [4aS, 9bR]-6-bromo-2,3,4,4a,5,9b- hexahydro-lH-pyrido[4,3-6]indole. A 100 mL round-bottomed flask is equipped with a magnetic stirring bar, a pressure-equalizing addition funnel, and a N₂ inlet on top of the addition funnel. The flask is charged with the S-mandelate starting material (5 g, 12.35 mmol), Na₂CO₃ (2.88 g, 27.17 mmol), and 25 mL of TηF. To the yellow reaction mixture at 25 ⁰C (heating block temperature) is added a solution of ethyl chloroformate (1.64 g, 15.11 mmol) in 5 mL of TηF dropwise over ca 70 minutes. The batch is stirred at 25 ⁰C for another 10 min, and is checked by ηPLC. Less than 2% of the starting material is observed by ηPLC, and the desired product is registered at ca. 98%. To the batch is added 12.5 mL of EtOH, and the batch is concentrated under reduced pressure to remove ca. 30 mL of solvent (mostly TηF). To the batch is then added 37.5 mL ofη₂O, and the resultant mixture shows pH >9 by pH paper. The yellow mixture is then stirred at rt for ca. 1 h, and is filtered. The solid is rinsed with 25 mL of H₂O. After drying in a vacuum oven at 58 ⁰C for ca. 16 h, 3.9442 g of a yellow solid is obtained (98% yield). ¹H NMR of the solid conformed, and showed no (s)-mandelic acid. HPLC analysis of the product shows the desired product at >99% purity. LC-MS showed a peak with M/e = 326 (M+ 1).