Hydrochloric Acid → N-Isobutyrylcysteine

HRID 2226908Notes

Reaction equation

HRID 2226908 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 6 h 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): δ1.2 (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): δ19, 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. stirringThe resulting mobile suspension was stirred for 6 h at room temperature
  3. temperaturefinally heated
  4. temperatureunder reflux for 4 h
  5. temperatureThe reaction mixture was cooled on an ice bath
  6. customThe organic phase was evaporated
  7. customto give a colourless oil
  8. washThe oil was washed with hexane
  9. additiontreated with ether
  10. customto give
  11. 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): δ1.2 (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-915ba405b7e74945b374be03f30d3119
Source dataset
uspto-grants-1994_09
Patent number
US05350767

Reaction notes

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