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

HRID 1520478Notes

Reaction equation

HRID 1520478 reaction equation
[CH2:1]([NH:3][CH2:4][C:5]1[N:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C@H:17]3[O:21]C(C)(C)[N:19]([C:24](=[O:28])[CH:25]([F:27])[F:26])[C@@H:18]3[CH2:29][F:30])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)[CH3:2].FC(F)(F)C(O)=O>C(Cl)Cl.C(=O)(O)[O-]>[CH2:1]([NH:3][CH2:4][C:5]1[N:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]([C@@H:17]([OH:21])[C@@H:18]([NH:19][C:24](=[O:28])[CH:25]([F:26])[F:27])[CH2:29][F:30])=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)[CH3:2]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866954361-{(4S,5R)-5-[4-(6-Ethylaminomethyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl}-2,2-difluoro-ethanone

Product 1

HCID 86695437N-{(1R,2R)-2-[4-(6-Ethylaminomethyl-pyridin-3-yl)-phenyl]-1-fluoromethyl-2-hydroxy-ethyl}-2,2-difluoro-acetamideYield 62.4%

Reagents, catalysts & solvents 2

HCID 769Bicarbonate IonSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-{(4S,5R)-5-[4-(6-Ethylaminomethyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl}-2,2-difluoro-ethanone (0.062 g, 0.147 mmol) in CH2Cl2 (5 mL) is added trifluoroacetic acid (1.0 mL) at room temperature. The resulting reaction mixture is stirred at room temperature for 5 hours. Solvent is evaporated in vacuo to get the crude residue and diluted with aqueous bicarbonate solution and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, concentrated and purified by combi-flash chromatography using 15% methanol in CH2Cl2 as an eluent. Obtained solid is washed with n-pentane and diethyl ether to afford the title compound (0.035 g) after drying in lypholizer. 1H NMR (400 MHz, DMSO-d6) δ: 1.16 (t, J=7.2 Hz, 3H), 2.83-2.88 (q, 2H), 4.14 (s, 2H), 4.30-4.33 (m, 1.5H), 4.41-4.45 (m, 0.5H), 4.55-4.56 (m, 0.5H), 4.65-4.68 (m, 0.5H), 4.89 (t, J=4.08 Hz, 1H), 5.93 (d, J=4.55 Hz, 1H), 6.20 (t, J=53.76 Hz, 1H), 7.47 (d, J=8.24 Hz, 2H), 7.54 (d, J=8.2 Hz, 1H), 7.72 (d, J=8.24 Hz, 2H), 8.12-8.15 (dd, J1=2.32 Hz, J2=8.16 Hz, 1H), 8.85 (d, J=8.8 Hz, 1H), 8.90 (d, J=2.12 Hz, 1H). LC-MS (m/z): [M+H]=382.1.

Workup

  1. customThe resulting reaction mixture
  2. customSolvent is evaporated in vacuo
  3. customto get the crude residue
  4. extractionextracted with ethyl acetate
  5. dry with materialOrganic layer is dried over sodium sulphate
  6. concentrationconcentrated
  7. custompurified by combi-flash chromatography
  8. customObtained solid
  9. washis washed with n-pentane and diethyl ether

Sources & evidence

ORD record
ord-3cd6c9131cba420d90bbf31567a2024a
Source dataset
uspto-grants-2015_07
Patent number
US09073894B2

Reaction notes

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