Dichloromethane → 4-bromo-N-[(1R)-1-cyclopropylethyl]-3-fluorobenzamide

HRID 2363284Notes

Reaction equation

HRID 2363284 reaction equation
C(N(CC)C(C)C)(C)C.[Br:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][C:12]=1[F:20].[CH:21]1([C@H:24]([NH2:26])[CH3:25])[CH2:23][CH2:22]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(Cl)Cl.C([O-])(O)=O.[Na+]>>[Br:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([NH:26][C@@H:24]([CH:21]2[CH2:23][CH2:22]2)[CH3:25])=[O:17])=[CH:13][C:12]=1[F:20]

Participants

7

Reactant 6

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 516892Sodium BicarbonateHCID 27733414-Bromo-3-fluorobenzoic acidHCID 7016286(R)-1-Cyclopropylethylamine

Product 1

HCID 712078924-bromo-N-[(1R)-1-cyclopropylethyl]-3-fluorobenzamideYield 95.4%

Procedure

N,N-Diisopropylethylamine (0.92 mL, 5.3 mmol) was added to a mixture of 4-bromo-3-fluorobenzoic acid (0.58 g, 2.6 mmol), (1R)-1-cyclopropylethanamine (0.27 mL, 2.9 mmol, Alfa Aesar: Cat. #H26902) and benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (1.3 g, 2.9 mmol) in methylene chloride (5.8 mL, 91 mmol). The reaction mixture was stirred at room temperature for 30 minutes, worked up with aqueous NaHCO3, and extracted with dichloromethylene (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-10%) to afford the desired product (0.71 g, 94%). LCMS (M+H)+: m/z=286.0/288.0.

Workup

  1. extractionextracted with dichloromethylene (3×20 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-10%)

Sources & evidence

ORD record
ord-8f16460e3b0e4985907046c183a83c63
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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