Hydrochloric Acid → N-Isobutyrylcysteine

HRID 2226916Notes

Reaction equation

HRID 2226916 reaction equation
O.Cl.[NH2:3][C@H:4]([C:7]([OH:9])=[O:8])[CH2:5][SH:6].O1CCCC1.[C:15]([O-])(=[O:19])[CH:16]([CH3:18])[CH3:17].[Na+].Cl>O>[C:15]([NH:3][C@H:4]([C:7]([OH:9])=[O:8])[CH2:5][SH:6])(=[O:19])[CH:16]([CH3:18])[CH3:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 23462L-Cysteine hydrochloride monohydrateHCID 23674499Sodium isobutyrate

Product 1

HCID 130211N-Isobutyrylcysteine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A suspension of 35.2 g (0.20 mol) of L-cysteine hydrochloride monohydrate in 100 ml of a mixture of 80% of tetrahydrofuran (THF) and 20% of water was stirred under nitrogen at room temperature and treated with 44.0 g (0.40 mol) of sodium isobutyrate. The reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen, 35 ml (0.21 mol) of isobutyryl anhydride was added dropwise. The resulting mobile suspension was stirred for 6h at room temperature, allowed to stand overnight, and finally heated under reflux for 4 h. The reaction mixture was cooled on an ice bath and 18 ml of concentrated hydrogen chloride was added. The organic phase was evaporated to give a colourless oil. The oil was washed with hexane and thereafter treated with ether to give 12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0, H2O, pH=7.0), 1H-NMR (CDCl3): δ 1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH). 13C-NMR (CDCl3): δ 19, 19.5; 26.5; 36; 54, 172, 178. ms: 335 (M+ +2TMS, after silylation).

Workup

  1. temperatureThe reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen
  2. temperaturefinally heated
  3. temperatureunder reflux for 4 h
  4. temperatureThe reaction mixture was cooled on an ice bath
  5. customThe organic phase was evaporated
  6. customto give a colourless oil
  7. washThe oil was washed with hexane
  8. additiontreated with ether
  9. customto give
  10. custom12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0, H2O, pH=7.0), 1H-NMR (CDCl3): δ 1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH)

Sources & evidence

ORD record
ord-77175d36266c4b18beebeda8e029d0d1
Source dataset
uspto-grants-1994_09
Patent number
US05350768

Reaction notes

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