Hydrochloric Acid → methyl (2S)-2-isocyanato-3,3-dimethylbutanoate

HRID 2377614Notes

Reaction equation

HRID 2377614 reaction equation
Cl.[CH3:2][C:3]([CH3:11])([CH3:10])[C@@H:4]([C:6]([O:8][CH3:9])=[O:7])[NH2:5].N1C=CC=CC=1.[C:18](Cl)(Cl)=[O:19].Cl>C(Cl)Cl>[CH3:2][C:3]([CH3:11])([CH3:10])[C@@H:4]([C:6]([O:8][CH3:9])=[O:7])[N:5]=[C:18]=[O:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 6371PhosgeneHCID 16217630Methyl L-tert-leucinate hydrochloride

Product 1

HCID 59856496methyl (2S)-2-isocyanato-3,3-dimethylbutanoateYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 3-methyl-L-valinate hydrochloride (10.0 g, 54.9 mmol) and pyridine (22.3 mL, 276 mmol) in methylenechloride (300 mL) was cooled in an ice bath under nitrogen. Phosgene (20% in toluene, 41.1 mL, 83.0 mmol) was added dropwise over 0.5 h using an addition funnel. The resulting mixture was stirred 1 h then poured into cold 1M hydrochloric acid and extracted with methylenechloride (3×100 mL). The combined organic extracts were washed with brine, dried with anhydrous magnesium sulfate, filtered and concentrated. Flash column chromatography eluting with hexane/ethyl acetate 90/10 gave methyl 3-methyl-N-(oxomethylene)-L-valinate as an orange oil, 6.99 g (74% yield).

Workup

  1. extractionextracted with methylenechloride (3×100 mL)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washFlash column chromatography eluting with hexane/ethyl acetate 90/10

Sources & evidence

ORD record
ord-b1ae9954ca1d443c8ed106f16b50b42c
Source dataset
uspto-grants-2008_12
Patent number
US07470664B2

Reaction notes

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