Methyl iodide → HCID 86728123, compound

HRID 627654Notes

Reaction equation

HRID 627654 reaction equation
[CH2:1]([C@H:4]1[C@:9]([C:11]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=2[F:20])([CH3:10])[N:8]=[C:7]([N:21]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:6]([CH3:37])([CH3:36])[S:5]1(=[O:39])=[O:38])[CH:2]=[CH2:3].[CH3:40][Si]([N-][Si](C)(C)C)(C)C.[K+].IC>C1COCC1>[CH2:1]([C:4]1([CH3:40])[S:5](=[O:38])(=[O:39])[C:6]([CH3:37])([CH3:36])[C:7]([N:21]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[N:8][C@@:9]1([C:11]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[CH:13][C:12]=1[F:20])[CH3:10])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86728121HCID 86728121, compound

Product 1

HCID 86728123HCID 86728123, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of tert-butyl N-[(2S,3R)-2-allyl-3-(2-fluoro-5-nitro-phenyl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]-N-tert-butoxycarbonyl-carbamate (0.22 g, 0.38 mmol) in THF (2 mL) at −78° C. was added potassium bis(trimethylsilyl)amide, 1M in THF (1.13 ml, 1.13 mmol) and the solution was stirred for 15 minutes. Iodomethane (0.070 ml, 1.13 mmol) was added and the mixture was stirred at −78° C. for 0.5 h. The reaction was quenched by water, extracted with ethyl acetate. The combined extracts were washed with brine, dried and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a BioTage column (25 g), eluting with a gradient of 5% to 40% EtOAc in hexane, to provide tert-butyl N-[(5R)-6-allyl-5-(2-fluoro-5-nitro-phenyl)-2,2,5,6-tetramethyl-1,1-dioxo-1,4-thiazin-3-yl]-N-tert-butoxycarbonyl-carbamate (0.19 g, 85% yield) as a white solid. m/z (ESI) 606.1 (M+Na)+.

Workup

  1. stirringthe mixture was stirred at −78° C. for 0.5 h
  2. customThe reaction was quenched by water
  3. extractionextracted with ethyl acetate
  4. washThe combined extracts were washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe crude material was absorbed onto a plug of silica gel
  8. custompurified by chromatography through a BioTage column (25 g)
  9. washeluting with a gradient of 5% to 40% EtOAc in hexane

Sources & evidence

ORD record
ord-7613097c766f4e18879d75c2a6d77903
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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