Trifluoroacetic acid → N-((1S,2R)-2-{4-[6-(1-Amino-2,2,2-trifluoro-ethyl)-pyridin-3-yl]-phenyl}-1-fluoromethyl-2-hydroxy-ethyl)-2,2-difluoro-acetamide

HRID 1520496Notes

Reaction equation

HRID 1520496 reaction equation
[NH2:1][CH:2]([C:7]1[N:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C@H:19]3[O:23]C(C)(C)[N:21]([C:26](=[O:30])[CH:27]([F:29])[F:28])[C@H:20]3[CH2:31][F:32])=[CH:15][CH:14]=2)=[CH:9][CH:8]=1)[C:3]([F:6])([F:5])[F:4].FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:1][CH:2]([C:7]1[N:12]=[CH:11][C:10]([C:13]2[CH:14]=[CH:15][C:16]([C@@H:19]([OH:23])[C@H:20]([NH:21][C:26](=[O:30])[CH:27]([F:29])[F:28])[CH2:31][F:32])=[CH:17][CH:18]=2)=[CH:9][CH:8]=1)[C:3]([F:4])([F:5])[F:6]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866954471-((4R,5R)-5-{4-[6-(1-Amino-2,2,2-trifluoro-ethyl)-pyridin-3-yl]-phenyl}-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl)-2,2-difluoro-ethanone

Product 1

HCID 86695448N-((1S,2R)-2-{4-[6-(1-Amino-2,2,2-trifluoro-ethyl)-pyridin-3-yl]-phenyl}-1-fluoromethyl-2-hydroxy-ethyl)-2,2-difluoro-acetamideYield 40.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1-((4R,5R)-5-{4-[6-(1-Amino-2,2,2-trifluoro-ethyl)-pyridin-3-yl]-phenyl}-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl)-2,2-difluoro-ethanone (35 mg, 0.076 mmol) in CH2Cl2 (1 mL) is added trifluoroacetic acid (1 mL) at 0° C. then stirred to room temperature for 3 hours. The solvent evaporated in vacuo and the crude material is diluted with ammonia solution and extract with ethyl acetate. Organic layer is dried over sodium sulphate, solvent is evaporated in vacuo and purified by preparative TLC using in 70% ethyl acetate in hexane to afford the title compound (0.013 g): 1H-NMR (400 MHz, DMSO-d6) δ: 2.66 (d, J=7.28 Hz, 2H), 4.30-4.36 (m, 1.5H), 4.40-4.44 (m, 0.5H), 4.54-4.55 (m, 0.5H), 4.61-4.68 (m, 1.5H), 4.89 (t, J=3.8 Hz, 1H), 5.93 (d, J=4.36 Hz, 1H), 6.19 (t, J=53.8 Hz, 1H), 7.45 (d, J=8.32 Hz, 2H), 8.00 (d, 1.16 Hz, 2H), 8.05 (d, J=8.28 Hz, 2H), 8.73 (s, 1H), 8.84 (d, J=8.56 Hz, 1H). LC-MS (m/z): [M+H]=422.0.

Workup

  1. customThe solvent evaporated in vacuo
  2. additionthe crude material is diluted with ammonia solution
  3. extractionextract with ethyl acetate
  4. dry with materialOrganic layer is dried over sodium sulphate, solvent
  5. customis evaporated in vacuo
  6. custompurified by preparative TLC

Sources & evidence

ORD record
ord-9545c62639d74750bd491a8c15094289
Source dataset
uspto-grants-2015_07
Patent number
US09073894B2

Reaction notes

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