Triethylamine → 1-(4-(Difluoromethyl)benzyl)-2-oxopyrrolidin-3-yl methanesulfonate

HRID 1507272Notes

Reaction equation

HRID 1507272 reaction equation
C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[F:13][CH:14]([F:29])[C:15]1[CH:28]=[CH:27][C:18]([CH2:19][N:20]2[CH2:24][CH2:23][C@H:22]([OH:25])[C:21]2=[O:26])=[CH:17][CH:16]=1>ClCCl.O>[CH3:8][S:9]([O:25][CH:22]1[CH2:23][CH2:24][N:20]([CH2:19][C:18]2[CH:17]=[CH:16][C:15]([CH:14]([F:13])[F:29])=[CH:28][CH:27]=2)[C:21]1=[O:26])(=[O:11])=[O:10]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 118207392(S)-1-(4-(Difluoromethyl)benzyl)-3-hydroxypyrrolidin-2-one

Product 1

HCID 1182074001-(4-(Difluoromethyl)benzyl)-2-oxopyrrolidin-3-yl methanesulfonateYield 66%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (0.319 mL, 2.29 mmol) and methansulfonyl chloride (0.131 mL, 1.68 mmol) was added to a stirred solution of (S)-1-(4-(difluoromethyl)benzyl)-3-hydroxypyrrolidin-2-one (368 mg, 1.53 mmol) in dichloromethane (7.63 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 h. The resulting mixture was diluted with water and the aqueous mixture was extracted with dichloromethane. The combined organic layers were washed with 10% sodium bicarbonate solution, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified using silica gel column chromatography (0-100% EtOAc). The pure fractions were combined and concentrated in vacuo to afford 1-(4-(difluoromethyl)benzyl)-2-oxopyrrolidin-3-yl methanesulfonate (322 mg, 66% yield) as a white solid: LC-MS (M+H)+320.1; 1H NMR (500 MHz, chloroform-d) δ 7.53 (d, J=7.9 Hz, 2H), 7.38-7.33 (m, 2H), 6.67 (br. t, J=1.0 Hz, 1H), 5.27 (dd, J=8.2, 7.5 Hz, 1H), 4.60-4.49 (m, 2H), 3.41-3.35 (m, 1H), 3.33 (s, 3H), 3.27 (dt, J=9.9, 7.3 Hz, 1H), 2.64-2.55 (m, 1H), 2.27 (ddt, J=13.9, 8.9, 7.1 Hz, 1H).

Workup

  1. extractionthe aqueous mixture was extracted with dichloromethane
  2. washThe combined organic layers were washed with 10% sodium bicarbonate solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-20f6e4749c344e65a8d98dff2f243498
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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