Triethylamine → (8aS)-7-(3-fluorobenzyl)-2-{[4-(trifluoromethyl)phenyl]sulfonyl}-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one

HRID 240460Notes

Reaction equation

HRID 240460 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[CH2:6][CH:7]1[C:15](=[O:16])[N:10]2[CH2:11][CH2:12][NH:13][CH2:14][C@@H:9]2[CH2:8]1.[F:20][C:21]([F:33])([F:32])[C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1.C(N(CC)CC)C>C(Cl)Cl>[F:2][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[CH2:6][CH:7]1[C:15](=[O:16])[N:10]2[CH2:11][CH2:12][N:13]([S:28]([C:25]3[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:32])[F:33])=[CH:27][CH:26]=3)(=[O:30])=[O:29])[CH2:14][C@@H:9]2[CH2:8]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27773994-(Trifluoromethyl)benzenesulfonyl chlorideHCID 86680468(8aS)-7-(3-fluorobenzyl)hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one hydrochloride

Product 1

HCID 86680470(8aS)-7-(3-fluorobenzyl)-2-{[4-(trifluoromethyl)phenyl]sulfonyl}-hexahydropyrrolo[1,2-a]pyrazin-6(2H)-oneYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product from Example 213B (20 mg, 0.070 mmol) was suspended in CH2Cl2 (0.5 mL), 4-(trifluoromethyl)benzene-1-sulfonyl chloride (21 mg, 0.084 mmol) and triethylamine (0.049 mL, 0.35 mmol) were added, and the resulting mixture was stirred at room temperature for 90 minutes. The mixture was partitioned between water and CH2Cl2, and the organic layer was dried over Na2SO4. The drying agent was removed by filtration, and the filtrate was concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-5% CH3OH in CH2Cl2 to give the title compound (30 mg, 94%). 1H NMR (300 MHz, CDCl3) δ ppm 1.16-1.51 (m, 1H) 1.59-1.72 (m, 1H) 1.88-2.03 (m, 1H) 2.09-2.32 (m, 1H) 2.64-3.12 (m, 4H) 3.27-3.64 (m, 1H) 3.73-3.86 (m, 2H) 4.11 (dd, J=13.22, 2.37 Hz, 1H) 6.68-6.98 (m, 3H) 7.08-7.29 (m, 1H) 7.77-7.89 (m, 4H); MS (ESI) m/z 457 (M+H)+.

Workup

  1. customThe mixture was partitioned between water and CH2Cl2
  2. dry with materialthe organic layer was dried over Na2SO4
  3. customThe drying agent was removed by filtration
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-5% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-187237cc9fe9404394c6f4aee713aa10
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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