Methyl iodide → tert-butyl (4S,7S,10aS)-7-(methoxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate

HRID 529539Notes

Reaction equation

HRID 529539 reaction equation
[CH3:1]C(C)([O-])C.[K+].[OH:7][CH2:8][C@H:9]1[N:19]2[C@@H:13]([S:14][CH2:15][CH2:16][C@H:17]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:18]2=[O:20])[CH2:12][CH2:11][CH2:10]1.IC>C1COCC1>[CH3:1][O:7][CH2:8][C@H:9]1[N:19]2[C@@H:13]([S:14][CH2:15][CH2:16][C@H:17]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:27])[CH3:26])[C:18]2=[O:20])[CH2:12][CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 23665647Potassium tert-butoxideHCID 68310946tert-butyl (4S,7S,10aS)-7-(hydroxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate

Product 1

HCID 86706224tert-butyl (4S,7S,10aS)-7-(methoxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamateYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of potassium tert-butoxide (1 M in THF, 1.55 mL, 1.55 mmol) was added dropwise to a 0° C. solution of tert-butyl (4S,7S,10aS)-7-(hydroxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (513 mg, 1.55 mmol) in THF (5 mL). The reaction mixture turned yellow in color. After 15 min of stirring, iodomethane (441 mg, 3.10 mmol) was added. The ice bath was removed and the reaction mixture was stirred at rt overnight. Water was added to the reaction and the mixture was concentrated to remove most of the THF. The aqueous solution was then extracted with EtOAc. The organic phase was isolated, washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-60% EtOAc/Hex to give tert-butyl (4S,7S,10aS)-7-(methoxymethyl)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepin-4-ylcarbamate (83 mg, 0.24 mmol, 16% yield) as a colorless oil. Anal. Calcd. for C16H28N2O4S m/z 344.4. found: 345.1 (M+H)+.

Workup

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred at rt overnight
  3. additionWater was added to the reaction
  4. concentrationthe mixture was concentrated
  5. customto remove most of the THF
  6. extractionThe aqueous solution was then extracted with EtOAc
  7. customThe organic phase was isolated
  8. washwashed with saturated aqueous NaCl
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product was purified
  13. washeluting with a gradient of 0-60% EtOAc/Hex

Sources & evidence

ORD record
ord-7fb1ddf67f87457c8497eac7623a9794
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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