Benzoyl chloride → HCID 49793048, compound

HRID 1799215Notes

Reaction equation

HRID 1799215 reaction equation
[C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:10][C:11]1[CH:12]=[C:13]([C@H:18]([CH2:23][NH:24]C(=O)C(F)(F)F)[CH2:19][C:20]([O-:22])=[O:21])[CH:14]=[CH:15][C:16]=1[Cl:17].C(N(C(C)C)CC)(C)C>ClCCl>[NH2:24][CH2:23][C@@H:18]([C:13]1[CH:14]=[CH:15][C:16]([Cl:17])=[C:11]([NH:10][C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:8])[CH:12]=1)[CH2:19][C:20]([OH:22])=[O:21]

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 81531Diisopropylethylamine2×HCID 86646669HCID 86646669, compound2×

Product 1

HCID 49793048HCID 49793048, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

At 0° C., 0.65 mmol of benzoyl chloride was slowly added to (3R)-3-(3-amino-4-chlorophenyl)-4-(2,2,2-trifluoroacetylamino)butanoate (200 mg, 0.59 mmol) (65b), the diisopropylethylamine (1.13 mL, 0.65 mmol) of (3R)-3-(3-amino-4-chlorophenyl)-4-(2,2,2-trifluoroacetylamino)butanoate, and 113 mL (0.65 mmol) of diisopropylethyl amine in 15 mL of dichloromethane. The reaction solution was stirred for 3 h at room temperature. The reaction mixture was then washed with 1N HCl and saturated sodium bicarbonate solution. The solvent was removed under reduced pressure. The residue, methyl (3R)-3-[3-(acetylamino)-4-chlorophenyl]-4-(2,2,2-trifluoroacetylamino)butanoate, was dissolved in 2.5 mL of methanol and 0.2 mL 2N sodium hydroxide. The solution was stirred at room temperature for 16 h. The solvent was removed under reduced pressure. The residue was purified by preparative HPLC to provide the title compound (65). 1H NMR (400 MHz, CD3OD): δ7.97 (d, J=8.0 Hz, 2H), 7.69 (s, 1H), 7.63-7.59 (m, 1H), 7.55-7.50 (m, 2H), 7.27 (d, J=8.0 Hz, 1H), 3.47-3.18 (m, 3H), 2.81 (dd, J=16.0, 8.0 Hz, 1H), 2.70 (dd, J=16.0, 8.0 Hz, 1H); MS (ESI) m/z 333.1 (M+H)+.

Workup

  1. washThe reaction mixture was then washed with 1N HCl and saturated sodium bicarbonate solution
  2. customThe solvent was removed under reduced pressure
  3. dissolutionThe residue, methyl (3R)-3-[3-(acetylamino)-4-chlorophenyl]-4-(2,2,2-trifluoroacetylamino)butanoate, was dissolved in 2.5 mL of methanol
  4. stirringThe solution was stirred at room temperature for 16 h
  5. customThe solvent was removed under reduced pressure
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-3b90f6ca022b4061abee96f7bb4e6335
Source dataset
uspto-grants-2013_01
Patent number
US08344028B2

Reaction notes

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