Water → Methanesulfonic acid 4'-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2'-fluoro-biphenyl-4-ylmethyl ester

HRID 857875Notes

Reaction equation

HRID 857875 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH:11]([CH2:13][NH:14][C:15](=[O:17])[CH3:16])[O:10][C:9]2=[O:18])[CH:5]=[CH:4][C:3]=1[C:19]1[CH:24]=[CH:23][C:22]([CH2:25][OH:26])=[CH:21][CH:20]=1.C(N(CC)CC)C.[CH3:34][S:35](Cl)(=[O:37])=[O:36].O>C(Cl)Cl>[C:15]([NH:14][CH2:13][CH:11]1[O:10][C:9](=[O:18])[N:8]([C:6]2[CH:5]=[CH:4][C:3]([C:19]3[CH:24]=[CH:23][C:22]([CH2:25][O:26][S:35]([CH3:34])(=[O:37])=[O:36])=[CH:21][CH:20]=3)=[C:2]([F:1])[CH:7]=2)[CH2:12]1)(=[O:17])[CH3:16]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 21907449N-[3-(2-Fluoro-4'-hydroxymethyl-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide

Product 1

HCID 86596639Methanesulfonic acid 4'-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2'-fluoro-biphenyl-4-ylmethyl esterYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 51 (12.49 g, 34.90 mmol) in methylene chloride (CH2Cl2, 150 mL) was treated with triethylamine (Et3N, 7.07 g, 9.7 mL, 70 mmol, 2.0 equiv) at 25° C., and the resulting mixture was cooled to 0–5° C. before being treated dropwise with methanesulfonyl chloride (4.80 g, 3.24 mL, 41.9 mmol, 1.2 equiv) at 0–5° C. The resulting reaction mixture was subsequently stirred at 0–5° C. for 2 h. When TLC and HPLC showed the reaction was complete, the reaction mixture was treated with H2O (100 mL) at 0–5° C. The mixture was then concentrated in vacuo to remove most of the CH2Cl2, and the resulting slurry was treated with H2O (150 mL). The mixture was stirred at room temperature for 10 min before being cooled to 0–5° C. for 30 min. The solid precipitates were collected by filtration, washed with H2O (2×100 mL) and 20% EtOAc/hexane (2×50 mL), and dried in vacuo. The crude desired methanesulfonic acid 4′-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl ester 52 (11.84 g, 78% yield) was obtained as off-white solids, which by TLC and HPLC was found to be essentially pure and was directly used in the subsequent reaction without further purification. LCMS (ESI) m/e 437 (M+H)+.

Workup

  1. temperaturethe resulting mixture was cooled to 0–5° C.
  2. customThe resulting reaction mixture
  3. concentrationThe mixture was then concentrated in vacuo
  4. customto remove most of the CH2Cl2
  5. additionthe resulting slurry was treated with H2O (150 mL)
  6. stirringThe mixture was stirred at room temperature for 10 min
  7. temperaturebefore being cooled to 0–5° C. for 30 min
  8. customThe solid precipitates
  9. filtrationwere collected by filtration
  10. washwashed with H2O (2×100 mL) and 20% EtOAc/hexane (2×50 mL)
  11. customdried in vacuo

Sources & evidence

ORD record
ord-e317d92daa7e40e98c823632f569e554
Source dataset
uspto-grants-2006_12
Patent number
US07148219B2

Reaction notes

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