Hydrochloric Acid → 5,5-Difluoro-4-[[(phenylmethoxy)carbonyl]amino]pentanoic acid
Reaction equation
[NH2:1][CH:2]([CH:8]([F:10])[F:9])[CH2:3][CH2:4][C:5]([OH:7])=[O:6].Cl[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13].Cl>[OH-].[Na+].O1CCOCC1>[CH2:15]([O:14][C:12]([NH:1][CH:2]([CH:8]([F:10])[F:9])[CH2:3][CH2:4][C:5]([OH:7])=[O:6])=[O:13])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1Participants
Procedure
To a solution of 2 mmole of 4-amino-4-difluoromethylbutyric acid in 5 ml of 1 N sodium hydroxide at 0° C. are added simultaneously from two syringes 2 mmole of benzyl chloroformate in 1 ml of dioxane and 2 ml of 1 N sodium hydroxide. After 30 minutes at 0° C. the solution is acidified by the addition of 6 N hydrochloric acid, then extracted well with dichloromethane. The organic phase is dried and concentrated to afford 4-benzyloxycarbonylamino-4-difluoromethylbutyric acid which is dissolved in 15 ml of dichloromethane and treated with 2 mmole of thionyl chloride at 25° C. for 1 hour after which 4 mmole of propyl amine is added. The solution is stirred at 25° C. for one hour, then washed with water, dried and concentrated. The residue is treated with 6 ml of a solution of dioxane containing 40% w/w hydrogen bromide and allowed to stand for 30 minutes at 25° C. after which 50 ml of ether is added. The resulting precipitate is collected to afford N-propyl 4-amino-4-difluoromethylbutyramide hydrobromide.
Workup
- extractionextracted well with dichloromethane
- customThe organic phase is dried
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-52b367a7d79041719f64bcae7b2e4db4
- Source dataset
- uspto-grants-1982_04
- Patent number
- US04326071
Reaction notes
Loading…