ChemicalBook CAS DataBase List D-1-N-BOC-PROLINAMIDE

D-1-N-BOC-PROLINAMIDE synthesis

5synthesis methods

Product Name:D-1-N-BOC-PROLINAMIDE
CAS Number:70138-72-6
Molecular formula:C10H18N2O3
Molecular Weight:214.26

37784-17-1

70138-72-6

General procedure for the synthesis of tert-butyl (R)-2-carbamoylpyrrolidine-1-carboxylate from Boc-D-proline: Example 1; Synthesis of tert-butyl (R)-2-carbamoylpyrrolidine-1-carboxylate. N-Methylmorpholine (9.85 g, 97.5 mmol) and isobutyl chloroformate (13.3 g, 97.5 mmol) were added to a THF solution (98 mL) of (R)-pyrrolidine-1,2-dicarboxylic acid 1- tert-butyl ester (20.0 g, 92.9 mmol) at -78 °C and stirred for 1 hour. Ammonium hydroxide (58 mL) was slowly added while the reaction system was warmed to room temperature and stirring was continued for 2 hours. Upon completion of the reaction, the reaction mixture was partitioned between dichloromethane and water. The organic phase was washed with 1 M HCl, dried over anhydrous sodium sulfate, filtered and concentrated to give the title product (10.8 g, 54%) as a colorless semi-solid.1H NMR (300 MHz, CDCl3): δ (ppm) 5.91-6.13 (m, 1H), 4.17-4.30 (m, 2H), 3.37-3.48 (m, 2H), 2.10- 2.18 (m, 2H), 1.84-1.96 (m, 2H), 1.45 (s, 9H).

37784-17-1 Synthesis

37784-17-1
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70138-72-6
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Yield:70138-72-6 54%

Reaction Conditions:

Stage #1:N-(tert-butoxycarbonyl)-D-proline with 4-methyl-morpholine;isobutyl chloroformate in tetrahydrofuran at -78; for 1 h;
Stage #2: with ammonia in tetrahydrofuran;water at -78 - 20; for 2 h;

Steps:

1
Example 1; (R)-2-Carbamoyl-pyrrolidine-1-carboxylic acid tert-butyl ester; N-Methylmorpholine (9.85 g, 97.5 mmol) and isobutyl chloroformate (13.3 g, 97.5 mmol) was added to (R)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (20.0 g, 92.9 mmol) in THF (200 mL) at -78° C. and stirred for 1 h. Ammonium hydroxide (58 mL) was added slowly as the reaction warmed up to RT and stirred for a further 2 h. The reaction mixture was partitioned between CH₂Cl₂and water. The organic extracts were washed with 1 M HCl, dried over sodium sulphate, filtered and concentrated to afford the title product (10.8 g, 54%) as a colourless semisolid.¹H NMR (300 MHz, CDCl₃): δ (ppm) 5.91-6.13 (m, 1H), 4.17-4.30 (m, 2H), 3.37-3.48 (m, 2H), 2.10-2.18 (m, 2H), 1.84-1.96 (m, 2H), 1.45 (s, 9H).

References:

AstraZeneca AB;NPS PHARMACEUTICALS, INC. US2007/259926, 2007, A1 Location in patent:Page/Page column 9

FullText

73323-65-6 Synthesis