Iodine → (S)-methyl 2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoate

HRID 20022

Reaction equation

HRID 20022 reaction equation
II.[C:3]([O:7][C:8]([C@H:10]([CH2:15]I)[C:11]([O:13][CH3:14])=[O:12])=[O:9])([CH3:6])([CH3:5])[CH3:4].I[C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1.C1(P(C2C=CC=CC=2C2C(OC)=CC=CC=2OC)C2CCCCC2)CCCCC1>CN(C=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:3]([O:7][C:8]([C@@H:10]([CH2:15][C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1)[C:11]([O:13][CH3:14])=[O:12])=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

8

Reactant 4

HCID 807IodineHCID 67993Benzene, 1-iodo-4-(trifluoromethyl)-HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86614124(R)-methyl2-(tert-butoxycarbonyl)-3-iodopropanoate

Product 1

HCID 67270692(S)-methyl 2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoate

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Iodine (0.0140 g, 0.0553 mmol) was added to zinc (0.542 g, 8.29 mmol) and the solid mixture was heated under vacuum for 10 minutes. The flask was flushed with nitrogen three times and allowed to cool. DMF (0.5 mL, degassed with nitrogen) was added and the suspension was cooled to 0° C. and stirred while (R)-methyl 2-(tert-butoxycarbonyl)-3-iodopropanoate (1.82 g, 5.53 mmol) in DMF (2.8 mL) was added dropwise. The mixture was stirred for 30 minutes at 0° C. and then allowed to come to RT for 30 minutes. 1-Iodo-4-(trifluoromethyl)benzene (1.50 g, 5.53 mmol), tris(dibenzylideneacetone)dipalladium (0.101 g, 0.111 mmol), and dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (S-Phos) (0.182 g, 0.442 mmol) were added. The flask was purged with nitrogen and heated at 40° C. After 3 hours the reaction was allowed to cool and partitioned between EtOAc and an aqueous solution of ˜9:1 saturated ammonium chloride/ammonium hydroxide. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with water, brine, and dried over sodium sulfate. Concentration and purification by silica gel chromatography (6:1 Hexanes/EtOAc) afforded (S)-methyl 2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoate.

Workup

  1. temperaturethe solid mixture was heated under vacuum for 10 minutes
  2. customThe flask was flushed with nitrogen three times
  3. temperatureto cool
  4. additionDMF (0.5 mL, degassed with nitrogen) was added
  5. additionwas added dropwise
  6. waitto come to RT for 30 minutes
  7. customThe flask was purged with nitrogen
  8. temperatureheated at 40° C
  9. waitAfter 3 hours the reaction was allowed
  10. temperatureto cool
  11. custompartitioned between EtOAc
  12. extractionThe aqueous layer was extracted with EtOAc
  13. washthe combined organic layers were washed with water, brine
  14. dry with materialdried over sodium sulfate
  15. concentrationConcentration and purification by silica gel chromatography (6:1 Hexanes/EtOAc)

Sources & evidence

ORD record
ord-deac4b6a5b2c4becbb470e5fb1bdccf9
Source dataset
uspto-grants-2010_06
Patent number
US07745484B2

Linked notes

Loading…