Triethylamine → (S)-1-(4-chlorobenzyl)-2-oxopyrrolidin-3-yl methanesulfonate

HRID 1507282Notes

Reaction equation

HRID 1507282 reaction equation
C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[Cl:13][C:14]1[CH:27]=[CH:26][C:17]([CH2:18][N:19]2[CH2:23][CH2:22][C@H:21]([OH:24])[C:20]2=[O:25])=[CH:16][CH:15]=1>ClCCl.O>[CH3:8][S:9]([O:24][C@H:21]1[CH2:22][CH2:23][N:19]([CH2:18][C:17]2[CH:16]=[CH:15][C:14]([Cl:13])=[CH:27][CH:26]=2)[C:20]1=[O:25])(=[O:11])=[O:10]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 118207417(S)-1-(4-chlorobenzyl)-3-hydroxypyrrolidin-2-one

Product 1

HCID 118207428(S)-1-(4-chlorobenzyl)-2-oxopyrrolidin-3-yl methanesulfonateYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (0.825 mL, 5.92 mmol) and methansulfonyl chloride (0.338 mL, 4.34 mmol) was added to a stirred solution of (S)-1-(4-chlorobenzyl)-3-hydroxypyrrolidin-2-one (890 mg, 3.94 mmol) in dichloromethane (20 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 (S)-1-(4-chlorobenzyl)-2-oxopyrrolidin-3-yl methanesulfonate (1.1 g, 3.62 mmol, 92% yield) as a white solid: LC-MS (M+H)+ 304.1; 1H NMR (500 MHz, chloroform-d) δ 7.38-7.33 (m, 2H), 7.22-7.17 (m, 2H), 5.25 (dd, J=8.2, 7.6 Hz, 1H), 4.52-4.41 (m, 2H), 3.40-3.31 (m, 4H), 3.25 (dt, J=10.0, 7.3 Hz, 1H), 2.58 (dddd, J=13.7, 8.4, 7.5, 3.3 Hz, 1H), 2.33-2.20 (m, 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-03e907b4a5cd41a8acd806a11e10e369
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

Loading…