Ethyl Acetate → (R)-ethyl 2-(4-amino-4-(5-bromo-2-fluorophenyl)-3,3-difluoro-2-methylpentan-2-yloxy)acetate

HRID 1186159Notes

Reaction equation

HRID 1186159 reaction equation
FC(F)(F)S(O)(=O)=O.[Br:9][C:10]1[CH:11]=[CH:12][C:13]([F:39])=[C:14]([C@:16]([NH:31]S(C(C)(C)C)(=O)=O)([CH3:30])[C:17]([F:29])([F:28])[C:18]([CH3:27])([O:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH3:19])[CH:15]=1.CCOC(C)=O>ClCCl.CCCCCCC>[NH2:31][C@@:16]([C:14]1[CH:15]=[C:10]([Br:9])[CH:11]=[CH:12][C:13]=1[F:39])([CH3:30])[C:17]([F:28])([F:29])[C:18]([CH3:27])([O:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH3:19]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 62406Trifluoromethanesulfonic acidHCID 70170158(R)-ethyl 2-(4-(5-bromo-2-fluorophenyl)-4-(1,1-dimethylethylsulfonamido)-3,3-difluoro-2-methylpentan-2-yloxy)acetate

Product 1

HCID 58562965(R)-ethyl 2-(4-amino-4-(5-bromo-2-fluorophenyl)-3,3-difluoro-2-methylpentan-2-yloxy)acetateYield 88.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8900HeptaneSolvent

Procedure

Dropwise addition of TRIFLUOROMETHANESULFONIC ACID in CH2Cl2 0.25 M (225 ml, 56.3 mmol, Eq: 3) to a solution of (R)-ethyl 2-(4-(5-bromo-2-fluorophenyl)-4-(1,1-dimethylethylsulfonamido)-3,3-difluoro-2-methylpentan-2-yloxy)acetate (RO5545483-000-005) (10 g, 18.8 mmol, Eq: 1.00) in Dichloromethane (188 ml) at 0° C. this reaction mixture was stirred at room temperature for 30 minutes Extracted with sat NaHCO3, CH2Cl2, dried over Na2SO4, filtered off, evaporated, dried in HV to give a brown oil (8.8 g; 114%) The residue was chromatographed, 50 g SiO2 (Flashmaster) with EtOAc 0%-50% in heptane to give (R)-ethyl 2-(4-amino-4-(5-bromo-2-fluorophenyl)-3,3-difluoro-2-methylpentan-2-yloxy)acetate (6.85 g, 16.6 mmol, 88.5% yield) as a light yellow oil.

Workup

  1. extractionExtracted with sat NaHCO3, CH2Cl2
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered off
  4. customevaporated
  5. customdried in HV
  6. customto give a brown oil (8.8 g; 114%) The residue
  7. customwas chromatographed

Sources & evidence

ORD record
ord-7a73d4827c47466eb974d7f4acbcbac0
Source dataset
uspto-grants-2014_03
Patent number
US08673894B2

Reaction notes

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