Pyridine → Methyl (S)-(-)-2-Isocyanato-3-methylbutyrate

HRID 1095288Notes

Reaction equation

HRID 1095288 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:10])[C@H:5]([CH:7]([CH3:9])[CH3:8])[NH2:6].N1C=CC=CC=1.[C:17](Cl)(Cl)=[O:18].C1(C)C=CC=CC=1>C(Cl)Cl>[O:18]=[C:17]=[N:6][C@H:5]([C:4]([O:3][CH3:2])=[O:10])[CH:7]([CH3:9])[CH3:8]

Participants

6

Reactant 4

HCID 1049PyridineHCID 1140TolueneHCID 6371PhosgeneHCID 111190Methyl valinate hydrochloride

Product 1

HCID 10397066Methyl (S)-(-)-2-Isocyanato-3-methylbutyrate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of L-valine methyl ester hydrochloride (10.0 g, 59.9 mmol), DCM (300 mL), and pyridine (19.3 mL, 240 mmol) was cooled in an ice/salt bath and a solution of 20% phosgene in PhMe (35.6 mL, 719 mmol) added dropwise, maintaining the reaction temperature below 5° C. during the addition. A white suspension resulted and after 1.5 hours, the reaction mixture was poured into ice-cold 1M HCl and extracted with DCM (2×500 mL). The combined organic phases were washed with brine, dried over anhydrous MgSO4, and evaporated. Flash column chromatography on silica (95 hexanes/5 EtOAc) gave the title compound as a colorless oil (6.43 g). 1H NMR (CDCl3 500 MHz) δ 3.94 (d, J=4.0 Hz, 1H), 3.82 (s, 3H), 2.24 (m, 1H), 1.03 (3, J=7.0 Hz, 3H), 0.90 (d, J=6.5 Hz, 3H) ppm.

Workup

  1. temperaturewas cooled in an ice/salt bath
  2. temperaturemaintaining the reaction temperature below 5° C.
  3. additionduring the addition
  4. customA white suspension resulted and after 1.5 hours
  5. extractionextracted with DCM (2×500 mL)
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. customevaporated

Sources & evidence

ORD record
ord-462caf95ce434945a3e885cf107e32b9
Source dataset
uspto-grants-2012_03
Patent number
US08138164B2

Reaction notes

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