tert-Butylsulfinamide, (R)-(+)- → HCID 86651612, compound

HRID 384016Notes

Reaction equation

HRID 384016 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:33])[C:16]([N:18]2[CH2:23][CH2:22][C:21](=O)[CH2:20][C@@H:19]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[CH3:32])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:36][C:37]([S@:40]([NH2:42])=[O:41])([CH3:39])[CH3:38]>C1COCC1.C(Cl)Cl.[Cl-].[Na+].O.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[F:12][C:9]([F:11])([F:10])[C:7]1[CH:6]=[C:5]([C@H:13]([N:15]([CH3:33])[C:16]([N:18]2[CH2:23][CH2:22][C:21](=[N:42][S:40]([C:37]([CH3:39])([CH3:38])[CH3:36])=[O:41])[CH2:20][C@@H:19]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[CH3:32])=[O:17])[CH3:14])[CH:4]=[C:3]([C:2]([F:34])([F:1])[F:35])[CH:8]=1

Participants

7

Reactant 2

HCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 11214272HCID 11214272, compound

Product 1

HCID 86651612HCID 86651612, compoundYield 45.6%

Reagents, catalysts & solvents 4

HCID 76524Titanium tetraethoxideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of (2R)—N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4-oxo-1-piperidinecarboxamide (WO0232867) (4 g, 7.93 mmol) and Titanium(IV) ethoxide (8 mL) in THF (10 mL) was added at 25° C., under Nitrogen, (R)-(+)-2-Methyl-2-propanesulfinamide (1.15 g, 9.52 mmol, Aldrich) and the reaction mixture was heated to 100° C. It was stirred at this temperature for 3 hrs, then it was diluted with DCM and brine (2 mL) was added. A white precipitate was formed and it was filtered-off. The resulting solution was dried (Na2SO4) and evaporated to dryness. The crude was purified by silica cartridge (25 g) (from 1:0 to 0:1 Cyclohexane/EtOAc) to give the title compound (2.2 g, 3.62 mmol, 45% yield) as a yellow gum. A further purification of the crude fractions containing the desired compound by flash chromatography on Companion CombiFlash (from 1:0 to 0:1 Cyclohexane/EtOAc) gave further title compound (848 mg, 1.40 mmol, 17.6% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 7.68-8.07 (m, 3H) 6.70-7.43 (m, 3H) 4.80-5.35 (m, 2H) 3.10-3.79 (m, 2H) 2.42-2.95 (m, 7H) 2.19-2.30 (m, 3 H) 1.46-1.62 (m, 3H) 1.01-1.22 (m, 9H); mixture of E+Z isomers

Workup

  1. additionwas added
  2. customA white precipitate was formed
  3. dry with materialThe resulting solution was dried (Na2SO4)
  4. customevaporated to dryness
  5. customThe crude was purified by silica cartridge (25 g) (from 1:0 to 0:1 Cyclohexane/EtOAc)

Sources & evidence

ORD record
ord-8f3109c95072445ca674348d9bb681b0
Source dataset
uspto-grants-2013_02
Patent number
US08367692B2

Reaction notes

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