4-Methylbenzenethiol → (6R,7aS)-6-p-Tolylsulfanyl-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one

HRID 455260Notes

Reaction equation

HRID 455260 reaction equation
[Na].[CH3:2][C:3]1[CH:8]=[CH:7][C:6]([SH:9])=[CH:5][CH:4]=1.Br[C@@H:11]1[CH2:30][N:14]2[C:15](=[O:29])[N:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)[CH2:17][C@@H:13]2[CH2:12]1>>[C:3]1([CH3:2])[CH:8]=[CH:7][C:6]([S:9][C@H:11]2[CH2:30][N:14]3[C:15](=[O:29])[N:16]([C:18]4[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=4)[CH2:17][C@@H:13]3[CH2:12]2)=[CH:5][CH:4]=1

Participants

4

Reactant 3

HCID 78114-MethylbenzenethiolHCID 5360545SodiumHCID 86673574(6S,7aS)-6-Bromo-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one

Product 1

HCID 70976100(6R,7aS)-6-p-Tolylsulfanyl-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-oneYield 893.6%

Procedure

Na (112 mg, 0.548 mmol) was added to anhydrous enthanol (10 ml). Until the sodium was dissolved. 4-methylbenzenethiol (34 mg, 0.0274 mmol) was added in the ice-bath. Subsequently (6S,7aS)-6-Bromo-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one (100 mg, 0.274 mmol) was added. After the addition, the ice bath was removed and the reaction was stirred for overnight at the room temperature. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to yield 100 mg (85%) of the title compounds as white solid. 1H NMR (300 MHz, CDCl3): δ 7.61-7.56 (m, 2H), 7.33-7.29 (m, 2H), 7.20-7.12 (m, 4H), 4.28-4.00 (m, 3H), 3.85-3.83 (m, 1H), 3.69 (dd, 1H, J1=2.7 Hz, J2=9.6 Hz), 3.11 (dd, 1H, J1=4.2 Hz, J2=12.9 Hz), 2.32 (s, 3H), 2.19-2.12 (m, 1H), 1.93-1.83 (m, 1H); LC-MS: 409 [M+1]+.

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-2f3aad1ada594528838cdd8c77e42511
Source dataset
uspto-grants-2013_07
Patent number
US08497288B2

Reaction notes

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