ChemicalBook CAS DataBase List N-CBZ-CIS-4-HYDROXY-D-PROLINE METHYL ESTER

N-CBZ-CIS-4-HYDROXY-D-PROLINE METHYL ESTER synthesis

11synthesis methods

Product Name:N-CBZ-CIS-4-HYDROXY-D-PROLINE METHYL ESTER
CAS Number:155075-23-3
Molecular formula:C14H17NO5
Molecular Weight:279.29

2584-71-6

N-CBZ-CIS-4-HYDROXY-D-PROLINE METHYL ESTER

155075-23-3

General procedure for the synthesis of (4R)-N-CBZ-4-hydroxy-D-proline methyl ester from cis-4-hydroxy-D-proline: to a stirred 4R-hydroxypyrrolidine-2R-carboxylic acid (5.02 g, 38.3 mmol, 1 eq.) and sodium bicarbonate (8.05 g, 95.8 mmol, 2.5 eq.) in water (85 mL) at 23°C was A solution of benzyl chloroformate (6.28 mL, 44.0 mmol, 1.15 eq.) in toluene (20 mL) was added slowly over 15 minutes. After 24 hours of reaction, the organic and aqueous layers were separated, the aqueous layer was extracted with ether (2 x 100 mL), and the organic layers were combined and discarded. Subsequently, the aqueous layer was acidified to pH 2 with concentrated hydrochloric acid and the product was extracted with ethyl acetate (2 x 100 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated in vacuum to give (4R)-N-benzyloxycarbonyl-4-hydroxy-D-proline methyl ester (9.97 g, 100% yield).

2584-71-6 Synthesis

2584-71-6
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$6.00/1g

155075-23-3
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$29.00/250mg

Yield: 100%

Reaction Conditions:

with sodium hydrogencarbonate in water;toluene at 23; for 24.25 h;

Steps:

92.1 Preparation of 1-(3,4-dimethoxy-5-trifluoromethylthiobenzoyl)-4R-methoxypyrrolidine- 2R-carboxylic acid hydroxyamide; Step 1
To a stirred solution of 4R-hydroxypyrrolidine-2R-carboxylic acid (5.02 g, 38.3 mmol, 1 eq. ) and [NAHC03] (8.05 g, 95.8 mmol, 2.5 eq. ) in H20 (85 mL) at 23 [°C] was added a solution of Cbz-Cl (6.28 mL, 44.0 mmol, 1.15 eq. ) in toluene (20 mL) over 15 min period. After 24 h the layers were separated and the aqueous layer was extracted with Et2O (2 x 100 mL) and discarded the combined organic layer. The aqueous layer was then acidified to pH 2 with concentrated [HCI,] and the product was extracted with EtOAc (2 x 100 mL). The organic layer was dried and concentrated in vacuo to give [4R-HYDROXYPYRROLIDINE-1,] [2R-DICARBOXYLIC] acid [1-] benzyl ester 2-methyl ester (9.97 g, [100%)

References:

VICURON PHARMACEUTICALS, INC. WO2004/7444, 2004, A2 Location in patent:Page 139