4-Methylmorpholine → (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino)-4-methylpentanoic acid cyanomethylamide
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:16][C@@H:17]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:18]([OH:20])=O)[C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:41][CH2:42][C:43]#[N:44].P(O)([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C(OCC)(=O)C>[C:42]([CH2:43][NH:44][C:18](=[O:20])[C@@H:17]([NH:16][C@@H:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)[CH2:21][CH:22]([CH3:23])[CH3:24])#[N:41]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid (1.17 g, 2.86 mmol) in THF (20 mL) at −10° C. were added 4-methylmorpholine (0.315 mL, 2.86 mmol) and isobutyl chloroformate (0.371 mL, 2.86 mmol). The reaction mixture was stirred for 10 minutes, whereupon aminoacetonitrile hydrochloride (0.318 g, 3.43 mmol) was added, followed by 4-methylmorpholine (0.315 mL, 2.86 mmol). The solution was stirred for 90 minutes. Ethyl acetate (30 mL) and aqueous disodium phosphate (30 mL) were added. The organic phase was separated, washed with brine, dried over MgSO4, and evaporated to dryness. The product was purified on a short plug of silica gel (10-50% ethyl acetate/hexane gradient elution) to give (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid cyanomethylamide.
Workup
- additionwas added
- customThe organic phase was separated
- washwashed with brine
- dry with materialdried over MgSO4
- customevaporated to dryness
- customThe product was purified on a short plug of silica gel (10-50% ethyl acetate/hexane gradient elution)
Sources & evidence
- ORD record
- ord-4058e85466bd4fd888b99defeb2627f0
- Source dataset
- uspto-grants-2008_05
- Patent number
- US07375134B2
Reaction notes
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