Sodium Bicarbonate → O-(3-(t-Butoxycarbonyl)propanoyloxy)methyl S-ethyl carbonothioate

HRID 1397104

Reaction equation

HRID 1397104 reaction equation
[C:1]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])(=[O:7])[CH2:2][CH2:3][C:4]([O-:6])=[O:5].C([O-])(O)=O.[Na+].[C:18](=[O:25])([O:22][CH2:23]I)[S:19][CH2:20][CH3:21]>O.C(Cl)Cl>[C:18](=[O:25])([S:19][CH2:20][CH3:21])[O:22][CH2:23][O:5][C:4](=[O:6])[CH2:3][CH2:2][C:1]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 11436522133217-42-2HCID 22317022Butanedioic acid,1-(1,1-dimethylethyl) ester

Product 1

HCID 86666520O-(3-(t-Butoxycarbonyl)propanoyloxy)methyl S-ethyl carbonothioateYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent3×

Procedure

To a mixture of acid 1 (1.0 g, 5.74 mmol) in H2O (14.5 mL), and CH2Cl2 (14.5 mL) was added NaHCO3 (1.00 g, 11.9 mmol) and TBAHSO4 (1.95 g, 5.74 mmol). After stirring for 25 min, S-ethyl O-iodomethyl carbonothioate (1.10 g, 4.42 mmol, prepared according to Synthesis 1990, 1159) in CH2Cl2 (5 mL) was added. The biphasic reaction was stirred vigorously for 2 h 35 min and was diluted with water and CH2Cl2. The layers were separated, the organic layer was washed with water, 0.5 N HCl solution, saturated NaHCO3 solution, saturated NaCl solution, dried over Na2SO4, filtered and concentrated to dryness. The crude product was triturated with Et2O and the solids were removed by filtration and rinsed with small portions of Et2O. After concentration, the combined filtrates were purified by flash chromatography on silica gel, using 20% EtOAc in hexanes as eluent to furnish compound 2 (1.06 g, 82%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.33 (t, J=7.4 Hz, 3H), 1.44 (s, 9H), 2.54-2.58 (m, 2H), 2.63-2.66 (m, 2H), 2.89 (q, J=7.4 Hz, 2H), 5.62 (s, 2H).

Workup

  1. customThe biphasic reaction
  2. stirringwas stirred vigorously for 2 h 35 min
  3. customThe layers were separated
  4. washthe organic layer was washed with water, 0.5 N HCl solution, saturated NaHCO3 solution, saturated NaCl solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude product was triturated with Et2O
  9. customthe solids were removed by filtration
  10. washrinsed with small portions of Et2O
  11. concentrationAfter concentration
  12. customthe combined filtrates were purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-ade47d10bb5e45d1978d49b7d0759dc7
Source dataset
uspto-grants-2014_12
Patent number
US08901072B2

Linked notes

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