Benzene, 1-bromo-4-(trifluoromethyl)- → tert-Butyl {(1S)-1-methyl-2-oxo-2-[4-(trifluoromethyl)phenyl]ethyl}carbamate

HRID 13062Notes

Reaction equation

HRID 13062 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[C:12]([O:16][C:17]([NH:19][C@H:20]([C:22](N(OC)C)=[O:23])[CH3:21])=[O:18])([CH3:15])([CH3:14])[CH3:13]>C1COCC1>[CH3:21][C@H:20]([NH:19][C:17](=[O:18])[O:16][C:12]([CH3:15])([CH3:14])[CH3:13])[C:22](=[O:23])[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 11806530(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate

Product 1

HCID 59339706tert-Butyl {(1S)-1-methyl-2-oxo-2-[4-(trifluoromethyl)phenyl]ethyl}carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred mixture of isopropylmagnesium chloride-lithium chloride complex (14% wt 1 M solution, 726 mg, 5 mmol, 5 ml) and THF (5 ml) was added 1-bromo-4-(trifluoromethyl)benzene (1.125 g, 5 mmol) under argon. The stirring was continued at r.t. for 4 h. A solution of N2-(tert-butoxycarbonyl)-N-methoxy-N-methyl-L-alaninamide (232 mg, 1 mmol) in THF (10 ml) was added dropwise, and the stirring was continued overnight at r.t. Then the reaction mixture was quenched with sat. aq. NH4Cl (20 ml), and stirring was continued for 30 min. The layers were separated, the aqueous layer extracted with ethyl acetate (20 ml). The combined organic extracts were dried over Na2SO4, and the solvent was evaporated to give yellow partly crystalline product. Purification by flash chromatography on silica gel with n-heptane/ethyl acetate afforded colourless solid, 260 mg (82%).

Workup

  1. waitthe stirring was continued overnight at r.t
  2. customThen the reaction mixture was quenched with sat. aq. NH4Cl (20 ml)
  3. waitwas continued for 30 min
  4. customThe layers were separated
  5. extractionthe aqueous layer extracted with ethyl acetate (20 ml)
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. customthe solvent was evaporated
  8. customto give yellow partly crystalline product
  9. customPurification by flash chromatography on silica gel with n-heptane/ethyl acetate afforded colourless solid, 260 mg (82%)

Sources & evidence

ORD record
ord-8a4cdab86a1f4ce9b140666085edfa5f
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Reaction notes

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