반응 #155455

반응 방정식

Methyl chloroformate

DIEA

(S)-tert-butyl 2-amino-3-methylbutanoate hydrochloride

→

(S)-tert-butyl 2-(methoxycarbonylamino)-3-methylbutanoate

수율 99.3%

용매

THF

반응 조건

후처리

1. 1
   기타the cooling bath was removed
2. 2
   기타The solvent was removed under diminished pressure
3. 3
   기타the residue partitioned between EtOAc and water (1 L each)
4. 4
   세척The organic layer was washed with H2O (1 L) and brine (1 L)
5. 5
   건조dried (MgSO4)
6. 6
   여과filtered
7. 7
   농축concentrated under diminished pressure
8. 8
   세척eluting with hexanes (4 L) and 15:85 EtOAc/hexanes (4 L)

실험 절차

DIEA (137.5 mL, 0.766 mol) was added to a suspension of (S)-tert-butyl 2-amino-3-methylbutanoate hydrochloride (75.0 g, 0.357 mol) in THF (900 mL), and the mixture was cooled to 0° C. (ice/water bath). Methyl chloroformate (29.0 mL, 0.375 mol) was added dropwise over 45 min, the cooling bath was removed and the heterogeneous mixture was stirred at ambient temperature for 3 h. The solvent was removed under diminished pressure and the residue partitioned between EtOAc and water (1 L each). The organic layer was washed with H2O (1 L) and brine (1 L), dried (MgSO4), filtered and concentrated under diminished pressure. The crude material was passed through a plug of silica gel (1 kg), eluting with hexanes (4 L) and 15:85 EtOAc/hexanes (4 L) to afford (S)-tert-butyl 2-(methoxycarbonylamino)-3-methylbutanoate as a clear oil (82.0 g, 99% yield). 1H-NMR (500 MHz, DMSO-d6, δ=2.5 ppm) 7.34 (d, J=8.6, 1H), 3.77 (dd, J=8.6, 6.1, 1H), 3.53 (s, 3H), 1.94-2.05 (m, 1H), 1.39 (s, 9H), 0.83-0.92 (m, 6H). 13C-NMR (126 MHz, DMSO-d6, δ=39.2 ppm) 170.92, 156.84, 80.38, 60.00, 51.34, 29.76, 27.62, 18.92, 17.95. LC/MS: [M+Na]+ 254.17.

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