Hydrochloric Acid → N-[(1,1-Dimethylethoxy)carbonyl]-3-(methyldithio)-L-alanine

HRID 2208644Notes

Reaction equation

HRID 2208644 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][SH:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:15][S-:16].[Na+].II.Cl>O.C1COCC1.CCO>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][S:14][S:16][CH3:15])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 807IodineHCID 152319N-tert-ButyloxycarbonylcysteineHCID 4378561Sodium methanethiolate

Product 1

HCID 14402896N-[(1,1-Dimethylethoxy)carbonyl]-3-(methyldithio)-L-alanineYield 68%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

(R)-2-((tert-butoxycarbonyl)amino)-3-mercaptopropanoic acid (Boc-L-Cys-OH) (110 mg, 0.5 mmol) was dissolved in H2O/THF (50% v/v, 20 mL). To the solution was added sodium thiomethoxide (350 mg, 5.0 mmol) at 0° C. Then, a solution of iodine in 95% EtOH was added dropwise until the color of the reaction system changed from colorless to brown. The mixture was stirred for 5.5 h with warming to room temperature. After removing THF under reduced pressure, reaction mixture was neutralized by 1 N HCl aq. until pH 2-3. The solution was extracted with EtOAc. The extract was washed with saturated NaS2O4 aq. and brine, and dried over MgSO4. Concentration under reduced pressure followed by flash chromatography over silica gel in EtOAc/Hexanes/AcOH (75:25:1) gave Boc-L-Csm-OH (90.8 mg, 68% yield). 1H NMR (360 MHz, CDCl3) δ 5.34 (s, 1H), 4.63 (br, s, 1H), 3.26-3.16 (m, 2H), 2.43 (m, 3H), 1.47 (s, 9H); LRMS (ESI) m/z calcd for C9H18NO4S2 (M+H)+ 268.1. found 268.2.

Workup

  1. customAfter removing THF
  2. customunder reduced pressure, reaction mixture
  3. extractionThe solution was extracted with EtOAc
  4. washThe extract was washed with saturated NaS2O4 aq. and brine
  5. dry with materialdried over MgSO4
  6. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-3b9ae90225ef4508839197662031c20e
Source dataset
uspto-grants-2016_06
Patent number
US09376700B2

Reaction notes

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