Phosgene → 3(R)-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic Acid Tert-Butyl Ester

HRID 1016550Notes

Reaction equation

HRID 1016550 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH2:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[C:29](Cl)(Cl)=[O:30]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]2[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[NH:21][C:29]2=[O:30])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 8471TriethylamineHCID 59918925(R)-3-(2-Aminophenylamino)piperidine-1-carboxylic acid tertbutyl ester

Product 1

HCID 599189263(R)-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic Acid Tert-Butyl EsterYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3(R)-(2-Amino-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (52 mg, 0.18 mmol), Et3N (1.0 ml) in CH2Cl2 (1 ml) at 0° C. was added a solution of phosgene (20% in toluene, 0.1 ml). After stirring for 2 hr and evaporation of solvent, the residue was purified by chromatography (1%-2% MeOH in CH2Cl2) to give a colorless oil (34 mg, 60%). 1H-NMR (300 MHz, CDCl3) δ 7.80 (d, 1H), 4.20 (m, 3H), 3.50 (m, 1H), 2.75 (m, 1H), 2.65 (m, 1H), 2.10 (m, 1H), 1.90 (m, 1H), 1.70 (m, 1H), 1.50 (s, 9H) ppm; IR (film) 3067, 2975, 2935, 2858, 1745, 1692, 1612, 1487, 1423, 1383, 1347, 1266, 1246, 1158 cm−1; LRMS (calculated for C17H23N3O3-BOC)+ 217, found 217.

Workup

  1. customevaporation of solvent
  2. customthe residue was purified by chromatography (1%-2% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-32529033e5b149e29497f34cbbec0970
Source dataset
uspto-grants-2002_11
Patent number
US06476050B2

Reaction notes

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