Triethylamine → Methanesulfonic acid 5-{4-[(4S,5R)-3-(2,2-difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyridin-2-ylmethyl ester

HRID 525541Notes

Reaction equation

HRID 525541 reaction equation
[F:1][CH:2]([F:28])[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][OH:25])=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:27])[CH3:26])=[O:4].C(N(CC)CC)C.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>C(Cl)Cl.C(=O)(O)[O-]>[F:28][CH:2]([F:1])[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:23]=[CH:22][C:21]([CH2:24][O:25][S:37]([CH3:36])(=[O:39])=[O:38])=[N:20][CH:19]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:26])[CH3:27])=[O:4]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 866954302,2-Difluoro-1-{(4S,5R)-4-fluoromethyl-5-[4-(6-hydroxymethyl-pyridin-3-yl)-phenyl]-2,2-dimethyl-oxazolidin-3-yl}-ethanone

Product 1

HCID 86695429Methanesulfonic acid 5-{4-[(4S,5R)-3-(2,2-difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyridin-2-ylmethyl esterYield 66.3%

Reagents, catalysts & solvents 2

HCID 769Bicarbonate IonSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2,2-Difluoro-1-{(4S,5R)-4-fluoromethyl-5-[4-(6-hydroxymethyl-pyridin-3-yl)-phenyl]-2,2-dimethyl-oxazolidin-3-yl}-ethanone (1.1 g, 2.792 mmol) in CH2Cl2 (50 mL) is added triethyl amine (0.564 g, 5.584 mmol) followed by methanesulphonyl chloride (0.365 g, 3.071 mmol) at 0° C. then stirred for 30 minutes at 0° C. Reaction mixture is diluted with saturated 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 30% ethyl acetate in hexane as an eluent to afford the title compound (0.875 g). 1H-NMR (400 MHz, DMSO) δ: 1.53 (s, 3H), 1.60 (S, 3H), 3.30 (s, 3H), 4.54-4.58 (m, 0.5H), 4.60-4.70 (m, 1H), 4.82-4.83 (m, 0.5H), 4.90-4.94 (m, 1H), 5.28 (d, J=3.68 Hz, 1H), 5.36 (s, 2H), 6.64 (t, J=52.4 Hz, 1H), 7.61-7.64 (m, 3H), 7.82 (d, J=8.08 Hz, 2H), 8.19-8.21 (dd, J1=2.4 Hz, J2=8.16 Hz, 1H), 8.94 (d, 2.2 Hz, 1H). LC-MS (m/z): [M+H]=473.2.

Workup

  1. customReaction mixture
  2. extractionextracted with ethyl acetate
  3. dry with materialOrganic layer is dried over sodium sulphate, solvent
  4. customis evaporated in vacuo
  5. custompurified by combi-flash chromatography

Sources & evidence

ORD record
ord-1907d49ffd9e483890b57f77d5984536
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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