(R)-2,2-diallyl-5-(5-bromo-2-fluoro-phenyl)-4-(2,4-dimethoxy-benzyl)-5-methyl-1,1-dioxo-1lambda6-thiomorpholin-3-one → (R)-8-(5-bromo-2-fluoro-phenyl)-9-(2,4-dimethoxy-benzyl)-8-methyl-6,6-dioxo-6lambda6-thia-9-aza-spiro[4.5]dec-2-en-10-one

HRID 920159Notes

Reaction equation

HRID 920159 reaction equation
[CH2:1]([C:4]1([CH2:33][CH:34]=C)[S:9](=[O:11])(=[O:10])[CH2:8][C@:7]([C:13]2[CH:18]=[C:17]([Br:19])[CH:16]=[CH:15][C:14]=2[F:20])([CH3:12])[N:6]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=2[O:30][CH3:31])[C:5]1=[O:32])[CH:2]=C>ClCCl>[Br:19][C:17]1[CH:16]=[CH:15][C:14]([F:20])=[C:13]([C@@:7]2([CH3:12])[N:6]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=3[O:30][CH3:31])[C:5](=[O:32])[C:4]3([CH2:33][CH:34]=[CH:2][CH2:1]3)[S:9](=[O:11])(=[O:10])[CH2:8]2)[CH:18]=1

Participants

3

Reactant 1

HCID 90067160(R)-2,2-diallyl-5-(5-bromo-2-fluoro-phenyl)-4-(2,4-dimethoxy-benzyl)-5-methyl-1,1-dioxo-1lambda6-thiomorpholin-3-one

Product 1

HCID 90024531(R)-8-(5-bromo-2-fluoro-phenyl)-9-(2,4-dimethoxy-benzyl)-8-methyl-6,6-dioxo-6lambda6-thia-9-aza-spiro[4.5]dec-2-en-10-oneYield 79.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2,2-diallyl-5-(5-bromo-2-fluoro-phenyl)-4-(2,4-dimethoxy-benzyl)-5-methyl-1,1-dioxo-1λ6-thiomorpholin-3-one (610 mg, 1.08 mmol, Eq: 1.00) in dichloromethane (20.3 ml) was added under argon [1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium (Grubbs II catalyst) (45.7 mg, 53.8 μmol, Eq: 0.05). The reaction mixture was stirred at reflux for 4 hours. Evaporation and chromatography on 20 g silica gel with 0% to 50% ethyl acetate in heptane gave the (R)-8-(5-bromo-2-fluoro-phenyl)-9-(2,4-dimethoxy-benzyl)-8-methyl-6,6-dioxo-6λ6-thia-9-aza-spiro[4.5]dec-2-en-10-one (460 mg, 854 μmol, 79.3% yield) as a white foam. MS (ISP): m/z=538.2 [M+H]+ and 540.2 [M+2+H]+.

Workup

  1. temperatureat reflux for 4 hours
  2. customEvaporation and chromatography on 20 g silica gel with 0% to 50% ethyl acetate in heptane

Sources & evidence

ORD record
ord-bc2eb13827674aedbb5ca0ccb486855d
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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