Trifluoroacetic acid → 2,2-Difluoro-N-[(1R,2R)-1-fluoromethyl-2-(4-{6-[(3-fluoro-propylamino)-methyl]-pyridin-3-yl}-phenyl)-2-hydroxy-ethyl]-acetamide

HRID 1487476Notes

Reaction equation

HRID 1487476 reaction equation
[F:1][CH:2]([F:32])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[N:20][C:21]([CH2:24][NH:25][CH2:26][CH2:27][CH2:28][F:29])=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)[O:7]C1(C)C)=[O:4].FC(F)(F)C(O)=O>C(Cl)Cl>[F:32][CH:2]([F:1])[C:3]([NH:5][C@@H:9]([CH2:10][F:11])[C@@H:8]([C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:19]=[N:20][C:21]([CH2:24][NH:25][CH2:26][CH2:27][CH2:28][F:29])=[CH:22][CH:23]=2)=[CH:16][CH:17]=1)[OH:7])=[O:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866954312,2-Difluoro-1-[(4S,5R)-4-fluoromethyl-5-(4-{6-[(3-fluoro-propylamino)-methyl]-pyridin-3-yl}-phenyl)-2,2-dimethyl-oxazolidin-3-yl]-ethanone

Product 1

HCID 866954322,2-Difluoro-N-[(1R,2R)-1-fluoromethyl-2-(4-{6-[(3-fluoro-propylamino)-methyl]-pyridin-3-yl}-phenyl)-2-hydroxy-ethyl]-acetamideYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2,2-Difluoro-1-[(4S,5R)-4-fluoromethyl-5-(4-{6-[(3-fluoro-propylamino)-methyl]-pyridin-3-yl}-phenyl)-2,2-dimethyl-oxazolidin-3-yl]-ethanone (0.113 g, 0.249 mmol) in CH2Cl2 (5 mL) is added trifluoroacetic acid (1.0 mL) at 0° C. The resulting reaction mixture is stirred at room temperature for 5 hours. Solvent is evaporated under reduced pressure and the crude residue is diluted with aqueous bicarbonate solution and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, solvent is evaporated in vacuo and purified by combi-flash chromatography using 15% methanol in CH2Cl2 as eluent. Obtained solid is further washed with n-pentane and diethyl ether to give the title compound (0.034 g). 1H NMR (400 MHz, DMSO-d6) δ: 1.84-1.93 (m, 2H), 2.50-2.54 (m, 2H), 2.76 (bs, 1H), 3.99 (bs, 2H), 4.29-4.31 (m, 1.5H), 4.40-4.48 (m, 1.5H), 4.54-4.60 (m, 1.5H), 4.65-4.68 (m, 0.5H), 4.87 (bs, 1H), 5.92 (d, J=4.52 Hz, 1H), 6.20 (t, J=53.64 Hz, 1H), 7.46 (d, J=8.24 Hz, 2H), 7.52 (d, J=8.12 Hz, 1H), 7.70 (d, J=8.24 Hz, 2H), 8.08-8.10 (dd, J1=2.36 Hz, J2=8.2 Hz, 1H), 8.85 (m, 2H). LC-MS (m/z): [M+H]=414.1.

Workup

  1. customThe resulting reaction mixture
  2. customSolvent is evaporated under reduced pressure
  3. additionthe crude residue is diluted with aqueous bicarbonate solution
  4. extractionextracted with ethyl acetate
  5. dry with materialOrganic layer is dried over sodium sulphate, solvent
  6. customis evaporated in vacuo
  7. custompurified by combi-flash chromatography
  8. customObtained solid
  9. washis further washed with n-pentane and diethyl ether

Sources & evidence

ORD record
ord-5acb08035734439d9ac33b0972304663
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

Loading…