ChemicalBook CAS DataBase List (S)-tert-butyl (4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate

(S)-tert-butyl (4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate synthesis

5synthesis methods

Product Name:(S)-tert-butyl (4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate
CAS Number:1306763-30-3
Molecular formula:C15H18N2O2
Molecular Weight:258.32

24424-99-5 Synthesis

24424-99-5
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(R)-1-amino-2,3-dihydro-1H-indene-4-carbonitrile hydrochloride

1306763-29-0
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(S)-tert-butyl (4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate

1306763-30-3
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Yield: 84%

Reaction Conditions:

with triethylamine in dichloromethane at 0 - 20; for 2 h;

Steps:

52
[0458] (R )-tert-butyl 4-cyano-2, 3-dihydro-lH-inden-l-ylcarbamate (INT-52)[0459] To (R)-l-amino-2,3-dihydro-lH-indene-l-yl)-4-carbonitrile HC1 INT-50 (11.6 g, 59.6 mmol) in DCM (100 mL) at 0°C was added TEA (12.0 mL, 131.0 mmol). To the resulting solution was added a solution of Boc anhydride (14.3 g, 65.6 mmol) in DCM (30 mL) and the reaction mixture stirred at room temperature for 1.5 h. The reaction mixture was washed with brine, and the organic layers were dried over MgS0₄ and filtered. Additional DCM was added to a total volume of 250 mL and Norit (4.5 g) was added. The product was refluxed for 15 mins and the hot mixture filtered through a pad of celite / silica. The filtrate was concentrated and recrystallized from EA (50 mL) and hexane (150 mL) to produce 12.93 g (84%) of (R)-tert-butyl 4-cyano-2,3-dihydro-lH-inden-l-ylcarbamate INT-52 as an off-white solid. LCMS-ESI (m z) calculated for Ci₅H₁₈N₂0₂: 258.3; found 281.1 [M+Na]⁺, t_R = 3.45 min. Elemental Analysis determined for Ci₅H₁₈N₂0₂; C calculated = 69.74%; found = 69.98%. H calculated = 7.02%; found = 7.14%. N calculated = 10.84%; found = 10.89%. NMR (400 MHz, CDC1₃) 6 7.64 - 7.49 (m, 2H), 7.34 (dt, J = 7.7, 3.8, 1H), 5.36 - 5.20 (m, 1H), 4.78 (d, J = 6.8, 1H), 3.20 (ddd, J = 16.9, 8.9, 3.3, lH), 3.02 (dt, J = 25.4, 8.4, 1H), 2.82 - 2.53 (m, 1H), 1.88 (dq, J = 13.2, 8.6, 1H), 1.55 - 1.44 (m, 9H). ¹³C NMR (101 MHz, DMSO) δ 155.52, 146.68, 146.32, 130.89, 128.70, 127.63, 117.51, 107.76, 77.98, 55.09, 31.88, 29.11, 28.19. Chiral HPLC: (R)-tert-butyl 4-cyano-2,3-dihydro-lH-inden-l- ylcarbamate was eluted using 2.5% EtOH in hexanes: >99.9% ee, tR = 19.36 min.

References:

RECEPTOS, INC.;MARTINBOROUGH, Esther;BOEHM, Marcus, F.;YEAGER, Adam, Richard;TAMIYA, Junko;HUANG, Liming;BRAHMACHARY, Enugurthi;MOORJANI, Manisha WO2011/60389, 2011, A1 Location in patent:Page/Page column 92-93

15115-60-3 Synthesis