3-Bromo-4-fluorobenzoic acid → N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-bromo-4-fluorobenzamide

HRID 1612429Notes

Reaction equation

HRID 1612429 reaction equation
ON1C2C=CC=CC=2N=N1.[Br:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[F:21])[C:15]([OH:17])=O.[CH3:22][C:23]([CH3:44])([CH3:43])[CH2:24][CH2:25][NH:26][C:27](=[O:42])[C@H:28]([CH3:41])[CH2:29][C@H:30]([OH:40])[C@@H:31]([NH2:39])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CN(C=O)C.ClCCl>[CH2:32]([C@H:31]([NH:39][C:15](=[O:17])[C:14]1[CH:18]=[CH:19][C:20]([F:21])=[C:12]([Br:11])[CH:13]=1)[C@@H:30]([OH:40])[CH2:29][C@H:28]([C:27](=[O:42])[NH:26][CH2:25][CH2:24][C:23]([CH3:22])([CH3:43])[CH3:44])[CH3:41])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 705093-Bromo-4-fluorobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 68890142(2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide

Product 1

HCID 69589710N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-bromo-4-fluorobenzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

N-Cyclohexylcarbodiimide-N′-methyl polystyrene (265 mg @ 1.70 mmol/g; ex. Novabiochem) was treated with a solution of 1-hydroxybenzotriazole (0.45 mmol) in DMF (1.0 ml) followed by 3-bromo-4-fluorobenzoic acid (99 mg, 0.45 mmol), dichloromethane (1 ml) and (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide (D2) (90 mg, 0.30 mmol) in dichloromethane (0.5 ml)/DMF (0.5 ml). After stirring gently overnight at room temperature, methylisocyanate polystyrene (150 mg @ 1.80 mmol/g; ex. Novabiochem) and tris-(2-aminoethyl)-amine polystyrene (250 mg @ 3.20 mmol/g; ex. Novabiochem) were added and the mixture was stirred for a further 1.5 h. It was then filtered and the spent resins were washed with DMF and dichloromethane. The combined filtrates were evaporated to dryness and the residue was filtered through a short column of silica gel to give the title compound, 126 mg.

Workup

  1. stirringthe mixture was stirred for a further 1.5 h
  2. filtrationIt was then filtered
  3. washthe spent resins were washed with DMF and dichloromethane
  4. customThe combined filtrates were evaporated to dryness
  5. filtrationthe residue was filtered through a short column of silica gel

Sources & evidence

ORD record
ord-63d2b5a745ac4a549307f7ef50ece968
Source dataset
uspto-grants-2006_01
Patent number
US06992103B2

Reaction notes

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