Methanol → methyl (S)-2-amino-4,4-difluoropentanoate hydrochloride
Reaction equation
S(Cl)([Cl:3])=O.C(OC([NH:12][C@@H:13]([CH2:17][C:18]([F:21])([F:20])[CH3:19])[C:14]([OH:16])=[O:15])=O)(C)(C)C.[CH3:22]O>>[ClH:3].[NH2:12][C@@H:13]([CH2:17][C:18]([F:21])([F:20])[CH3:19])[C:14]([O:16][CH3:22])=[O:15]Participants
Conditions
- Temperature
- 35 °C
Procedure
At approx. 5° C. (ice bath cooling), 8.2 ml of thionyl chloride (112.6 mmol; 1.5 eq.) were added dropwise to 100 ml of methanol (p.a.) under argon. The mixture was allowed to come to RT within 30 min and stirred for a further 30 min. 19.0 g of (S)-2-tert-butoxycarbonylamino-4,4-difluoropentanoic acid (75.0 mmol) were added in portions to this reaction mixture. The reaction mixture was stirred at RT for 2 h. Thereafter, the reaction mixture was warmed to 35° C. (internal temperature) and stirred at this temperature for another 3 h. Subsequently, the mixture was concentrated under reduced pressure, which afforded methyl (S)-2-amino-4,4-difluoropentanoate hydrochloride as a slightly brownish crystalline solid which was clean enough for further reactions. Yield: 13.5 g (89% of theory).
Workup
- stirringThe reaction mixture was stirred at RT for 2 h
- stirringstirred at this temperature for another 3 h
- concentrationSubsequently, the mixture was concentrated under reduced pressure, which
Sources & evidence
- ORD record
- ord-3e2697fbfd564d99aaa8d01b8f26b28e
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08609681B2
Reaction notes
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