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

HRID 571472Notes

Reaction equation

HRID 571472 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-734fb3d2bb784c74b8e0a3b0a921da0b
Source dataset
uspto-grants-2015_05
Patent number
US09023840B2

Reaction notes

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