Sodium Bicarbonate → O-(3-(1,5-di(t-butoxycarbonyl)-3-(2-(t-butoxycarbonyl)ethyl)pentan-3-ylcarbamoyl)propanoyloxy)methyl S-ethyl carbonothioate

HRID 1397124Notes

Reaction equation

HRID 1397124 reaction equation
[C:1]([O:5][C:6]([CH2:8][CH2:9][C:10]([NH:29][C:30]([CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[O:31])([CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:11][CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])(O)=O.[Na+].[C:42](=[O:49])([O:46][CH2:47]I)[S:43][CH2:44][CH3:45]>O.C(Cl)Cl>[C:42](=[O:49])([S:43][CH2:44][CH3:45])[O:46][CH2:47][O:35][C:34](=[O:36])[CH2:33][CH2:32][C:30](=[O:31])[NH:29][C:10]([CH2:9][CH2:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])([CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:11][CH2:12][C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 11436522(Ethylsulfanyl)(iodomethoxy)methanoneHCID 866665363-(1,5-Di(t-butoxycarbonyl)-3-(2-(t-butoxycarbonyl)ethyl)pentan-3-ylcarbamoyl)propanoic acid

Product 1

HCID 86666537O-(3-(1,5-di(t-butoxycarbonyl)-3-(2-(t-butoxycarbonyl)ethyl)pentan-3-ylcarbamoyl)propanoyloxy)methyl S-ethyl carbonothioateYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent3×

Procedure

To a mixture of acid 73 (519 mg, 1.01 mmol) in H2O (3 mL) and CH2Cl2 (3 mL) was added NaHCO3 (176 mg, 2.09 mmol) and TBAHSO4 (342 mg, 1.01 mmol). After stirring for 20 min, S-ethyl O-iodomethyl carbonothioate (192 mg, 0.77 mmol) in CH2Cl2 (1 mL) was added. The biphasic reaction was stirred vigorously for 3 h and was diluted with water and CH2Cl2. The layers were separated and the organic layer was washed with H2O, 0.5 N HCl solution, saturated NaHCO3 solution, saturated NaCl solution, dried over MgSO4, 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 a Biotage™ flash chromatography system, using a gradient of 20-60% EtOAc in CH2Cl2 as eluent, to furnish compound 74 (351 mg, 72%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.33 (t, J=7.4 Hz, 3H), 1.44 (s, 27H), 1.94-1.98 (m, 6H), 2.20-2.24 (m, 6H), 2.43 (t, J=6.9 Hz, 2H), 2.70 (t, J=6.9 Hz, 2H), 2.89 (q, J=7.4 Hz, 2H), 5.81 (s, 2H), 5.98 (s, 1H).

Workup

  1. customThe biphasic reaction
  2. stirringwas stirred vigorously for 3 h
  3. customThe layers were separated
  4. washthe organic layer was washed with H2O, 0.5 N HCl solution, saturated NaHCO3 solution, saturated NaCl solution
  5. dry with materialdried over MgSO4
  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 a Biotage™ flash chromatography system

Sources & evidence

ORD record
ord-4c3b24b650684114a656e617d94b1fbe
Source dataset
uspto-grants-2014_12
Patent number
US08901072B2

Reaction notes

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