Water → (1S,2S)-2-phenyl-cyclopropanecarboxylic acid [(S)-1-(4-bromo-phenyl)-propyl]-amide

HRID 454964Notes

Reaction equation

HRID 454964 reaction equation
[C:1]1([C@H:7]2[CH2:9][C@@H:8]2[C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([C@@H:20]([NH2:23])[CH2:21][CH3:22])=[CH:16][CH:15]=1.C(N(CC)CC)C.O>ClCCl.CN(C)C=O>[Br:13][C:14]1[CH:15]=[CH:16][C:17]([C@@H:20]([NH:23][C:10]([C@H:8]2[CH2:9][C@@H:7]2[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:12])[CH2:21][CH3:22])=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 7785172-Phenyl-1-cyclopropanecarboxylic acid, (1S-trans)-HCID 7127717(S)-1-(4-bromophenyl)propan-1-amine

Product 1

HCID 67432459(1S,2S)-2-phenyl-cyclopropanecarboxylic acid [(S)-1-(4-bromo-phenyl)-propyl]-amideYield 92.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (1S,2S)-2-phenyl-cyclopropanecarboxylic acid (170 mg, 1.05 mmol) in dichloromethane (10 ml) was added oxallyl dichloride (145 mg, 1.2 mmol) followed by a few drops of N,N-dimethylformamide at RT. The reaction mixture was stirred at RT for 45 mins before it was concentrated down and dissolved in dichloromethane (1.5 ml). The solution was added slowly to a solution of (S)-1-(4-bromo-phenyl)-propylamine (250 mg, 1.0 mmol, HCl salt) and triethylamine (222 mg, 2.2 mmol) in dichloromethane (10 ml) at 0° C. The resulting reaction mixture was stirred at RT for 1.5 h. Water was added and the aqueous layer was extracted by dichloromethane. Organic layer was dried by magnesium sulfate and concentrated. The residue was purified via column chromatography on silica gel to afford (1S,2S)-2-phenyl-cyclopropanecarboxylic acid [(S)-1-(4-bromo-phenyl)-propyl]-amide (330 mg, 92%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.37 (d, J=8.6 Hz, 2H), 7.15-7.23 (m, 2H), 7.11 (d, J=7.3 Hz, 1H), 7.08 (d, J=8.3 Hz, 2H), 6.98 (d, J=7.3 Hz, 2H), 5.75 (d, J=7.6 Hz, 1H), 4.77 (q, J=7.5 Hz, 1H), 2.31-2.41 (m, 1H), 1.65-1.81 (m, 2H), 1.48-1.59 (m, 2H), 1.12-1.23 (m, 1H), 0.82 (t, J=7.4 Hz, 3H); LRMS (ESI) (M+1)=360.04. Molecular Formula=C19H20BrNO.

Workup

  1. concentrationwas concentrated down
  2. dissolutiondissolved in dichloromethane (1.5 ml)
  3. customThe resulting reaction mixture
  4. stirringwas stirred at RT for 1.5 h
  5. extractionthe aqueous layer was extracted by dichloromethane
  6. dry with materialOrganic layer was dried by magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified via column chromatography on silica gel

Sources & evidence

ORD record
ord-113f1d16fab24012a1c7329658d789c1
Source dataset
uspto-grants-2013_07
Patent number
US08497271B2

Reaction notes

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