Methyl chloroformate → 1-Piperidinecarboxylic acid, 3-[(R)-(3-chlorophenyl)[2-[(methoxycarbonyl)amino]ethoxy]methyl]-, 1,1-dimethylethyl ester, (3R)-

HRID 2266218Notes

Reaction equation

HRID 2266218 reaction equation
[NH2:1][CH2:2][CH2:3][O:4][C@@H:5]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=1)[C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1.CCN(CC)CC.Cl[C:34]([O:36][CH3:37])=[O:35]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:25][C:21]1[CH:20]=[C:19]([C@H:5]([O:4][CH2:3][CH2:2][NH:1][C:34]([O:36][CH3:37])=[O:35])[C@@H:6]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:7]2)[CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 59598469(R)-tert-butyl 3-((R)-(2-aminoethoxy)(3-chlorophenyl)methyl)piperidine-1-carboxylate

Product 1

HCID 595984981-Piperidinecarboxylic acid, 3-[(R)-(3-chlorophenyl)[2-[(methoxycarbonyl)amino]ethoxy]methyl]-, 1,1-dimethylethyl ester, (3R)-Yield 58.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-tert-butyl 3-((R)-(2-aminoethoxy)(3-chlorophenyl)methyl)piperidine-1-carboxylate (1.05 g, ca. 2.6 mmol), Et3N (3.96 mL, 2.85 mmol), and DMAP (174 mg, 1.43 mmol) in anhydrous CH2Cl2 (20 mL) cooled to 0° C. was added a solution of methyl chloroformate (1.35 g, 14.25 mmol) in dichloromethane (20 mL) within 30 min. The reaction was stirred overnight, and evaporated under vacuum. The residue was purified by flash chromatography on silica gel to afford (R)-tert-butyl 3-((R)-(3-chlorophenyl)(2-(methoxycarbonylamino)ethoxy)methyl)piperidine-1-carboxylate (0.65 g). MS: 427 (M+H)+.

Workup

  1. customevaporated under vacuum
  2. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-856556a246644848a68d4ec4ccad3a6b
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

Loading…