Methyl chloroformate → HCID 58209574, compound

HRID 625534Notes

Reaction equation

HRID 625534 reaction equation
CCN(C(C)C)C(C)C.Cl.[NH2:11][C@@H:12]([CH:20]([CH3:22])[CH3:21])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].Cl[C:24]([O:26][CH3:27])=[O:25]>C1COCC1>[CH3:27][O:26][C:24]([NH:11][C@@H:12]([CH:20]([CH3:22])[CH3:21])[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])=[O:25]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 12490702tert-butyl (2S)-2-amino-3-methylbutanoate hydrochloride

Product 1

HCID 58209574HCID 58209574, compoundYield 99.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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, 1 H), 3.77 (dd, J=8.6, 6.1, 1 H), 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.

Workup

  1. customthe cooling bath was removed
  2. customThe solvent was removed under diminished pressure
  3. customthe residue partitioned between EtOAc and water (1 L each)
  4. washThe organic layer was washed with H2O (1 L) and brine (1 L)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under diminished pressure
  8. washeluting with hexanes (4 L) and 15:85 EtOAc/hexanes (4 L)

Sources & evidence

ORD record
ord-ac4928436f204e059fa85bee882b4285
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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