2,6-Dichlorobenzoyl chloride → (S)-2-tert-butoxycarbonylamino-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl ester

HRID 1976946Notes

Reaction equation

HRID 1976946 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].C(N(C(C)C)CC)(C)C.[Cl:31][C:32]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[C:33]=1[C:34](Cl)=[O:35]>ClCCl.O>[CH3:1][O:2][C:3](=[O:21])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:34]([C:33]2[C:32]([Cl:31])=[CH:40][CH:39]=[CH:38][C:37]=2[Cl:41])=[O:35])=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:7]

Participants

6

Reactant 3

HCID 783922,6-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 110118554-Amino-N-((1,1-dimethylethoxy)carbonyl)-L-phenylalanine methyl ester

Product 1

HCID 54393861(S)-2-tert-butoxycarbonylamino-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl esterYield 100.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-amino-N-[(1,1-dimethylethoxyl)carbonyl]-L-phenylalanine methyl ester 2.6 g, 8.6 mmol) in dichloromethane (20 mL) were added diisopropylethylamine (2.3 mL, 13 mmol) followed by 2,6-dichlorobenzoyl chloride (1.99 g, 9.5 mmol) at room temperature. The mixture was stirred for 15 hr at which time a white precipitate formed. The mixture was diluted with 30 mL of dichloromethane and 50 mL of water. The layers were separated and the aqueous layer was extracted with dichloromethane (2×50 mL). The combined extracts were washed with brine and dried over anhydrous magnesium sulfate. Filtration and concentration of the solvent gave 4.03 g (quant) of 4-[(2,6-dichlorophenylcarbonyl)amino]-N-[(1,1-dimethylethoxyl)carbonyl]-L-phenylalanine methyl ester as a white solid: mp 148-151° C.

Workup

  1. customformed
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with dichloromethane (2×50 mL)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationFiltration and concentration of the solvent

Sources & evidence

ORD record
ord-99ef85d0e1e44c8a8b5d7b071d86be03
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

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