Water → 2,2-Difluoro-N-{(1S,2R)-1-fluoromethyl-2-hydroxy-2-[4-(6-pyrrolidin-2-yl-pyridin-3-yl)-phenyl]ethyl}-acetamide

HRID 525619Notes

Reaction equation

HRID 525619 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([C@H:25]3[O:29]C(C)(C)[N:27]([C:32](=[O:36])[CH:33]([F:35])[F:34])[C@@H:26]3[CH2:37][F:38])=[CH:21][CH:20]=2)=[CH:15][N:14]=1)=O)(C)(C)C.C(Cl)Cl.FC(F)(F)C(O)=O.O>C1(C)C=CC=CC=1>[F:35][CH:33]([F:34])[C:32]([NH:27][C@H:26]([CH2:37][F:38])[C@H:25]([OH:29])[C:22]1[CH:21]=[CH:20][C:19]([C:16]2[CH:15]=[N:14][C:13]([CH:9]3[CH2:10][CH2:11][CH2:12][NH:8]3)=[CH:18][CH:17]=2)=[CH:24][CH:23]=1)=[O:36]

Participants

6

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 866955072-(5-{4-[(4S,5R)-3-(2,2-Difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyridin-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 717356152,2-Difluoro-N-{(1S,2R)-1-fluoromethyl-2-hydroxy-2-[4-(6-pyrrolidin-2-yl-pyridin-3-yl)-phenyl]ethyl}-acetamideYield 58.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 2-(5-{4-[(4S,5R)-3-(2,2-Difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyridin-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 0.94 mmol) and CH2Cl2 (20 mL), cooled to 0° C., is added trifluoroacetic acid (3 mL) and water (100 ul). The reaction is allowed to warm to ambient temperature, and is stirred for a further 2 hours. Toluene (20 mL) is added and the reaction mixture concentrated under vacuum to give the crude product. Purification by preparative HPLC gave the title compound (217 mg): 1H NMR (400 MHz, CDCl3), 1.88-2.06 (m, 3H), 2.38-2.48 (m, 1H), 3.22-3.40 (m, 3H), 4.25-4.37 (m, 1.5H), 4.4-4.47 (m, 0.5H), 4.52-4.59 (m, 0.5H), 4.63-4.70 (m, 0.5H), 4.71-4.78 (m, 1H), 4.86-4.94 (m, 1H), 5.89-6.01 (m, 1H), 6.20 (t, 1H), 7.43-7.53 (m, 2H), 7.58-7.63 (1H, m), 7.71-7.77 (m, 2H), 8.15-8.24 (m, 1H), 8.82-8.88 (m, 1H), 8.9-8.94 (m, 1H). m/z M+H 394.

Workup

  1. concentrationthe reaction mixture concentrated under vacuum
  2. customto give the crude product
  3. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-54d101cc1543495192254950ea84343b
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

Loading…