L-Valine → (2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acid

HRID 1504304Notes

Reaction equation

HRID 1504304 reaction equation
[CH3:1][O:2][C:3](Cl)=[O:4].[NH2:6][C@@H:7]([CH:11]([CH3:13])[CH3:12])[C:8]([OH:10])=[O:9].[OH-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>O>[CH3:1][O:2][C:3]([NH:6][C@@H:7]([CH:11]([CH3:13])[CH3:12])[C:8]([OH:10])=[O:9])=[O:4]

Participants

6

Reactant 4

HCID 6287L-ValineHCID 6586Methyl chloroformateHCID 10340Sodium CarbonateHCID 14798Sodium Hydroxide

Product 1

HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidYield 93%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Methylchloroformate (14.5 mL, 0.188 mol) was added over 15 min to a cooled (0-6° C.) mixture of (S)-2-amino-3-methyl-butyric acid (20.0 g, 0.171 mol), NaOH (6.80 g, 0.171 mol) and sodium carbonate (18.1 g, 0.171 mol) in water (200 mL). The cooling bath was removed and the mixture was stirred at ambient temperature overnight. Conc. aqueous HCl (30 mL) was added to the reaction mixture to adjust pH to ˜1. A solid formed and the mixture was stirred for 90 min. The mixture was filtered and the solid was dried overnight under reduced pressure at 40° C. to provide the title intermediate (27.8 g, 93% yield). 1H NMR (CD3OD, 400 MHz) δ (ppm) 4.87 (br. s, 4H), 4.05 (d, J=5.49, 1 H), 3.65 (s, 3H), 2.25-2.05 (m, 1H), 0.98 (d, J=6.87, 3H), 0.94 (d, J=6.87, 3H).

Workup

  1. temperaturea cooled
  2. customThe cooling bath was removed
  3. additionConc. aqueous HCl (30 mL) was added to the reaction mixture
  4. customA solid formed
  5. stirringthe mixture was stirred for 90 min
  6. filtrationThe mixture was filtered
  7. customthe solid was dried overnight under reduced pressure at 40° C.

Sources & evidence

ORD record
ord-cec46f06f8dc4673b1eb89745c876a0d
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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