Allyl bromide → HCID 86728109, compound

HRID 627641Notes

Reaction equation

HRID 627641 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[C:21]([CH3:23])([CH3:22])[S:20](=[O:25])(=[O:24])[CH2:19][C@@:18]([CH2:36][F:37])([C:26]2[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:27]=2[F:35])[N:17]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:48](Br)[CH:49]=[CH2:50]>C1COCC1>[CH2:50]([CH:19]1[C@@:18]([CH2:36][F:37])([C:26]2[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:27]=2[F:35])[N:17]=[C:16]([N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:12])[CH3:13])[C:21]([CH3:23])([CH3:22])[S:20]1(=[O:25])=[O:24])[CH:49]=[CH2:48]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 86728110HCID 86728110, compound

Product 1

HCID 86728109HCID 86728109, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of tert-butyl N-tert-butoxycarbonyl-N-[(3S)-3-(fluoromethyl)-3-(2-fluoro-5-nitro-phenyl)-6,6-dimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]carbamate (2.79 g, 5.10 mmol) in THF (30 mL) at −78° C. under a nitrogen atmosphere was added lithium bis(trimethylsilyl)amide, (7.65 mL, 7.65 mmol, 1M in THF) dropwise. The reaction mixture was stirred at −78° C. for 1 h and then allyl bromide (1.77 mL, 20.41 mmol) was added dropwise. The reaction mixture was stirred at −78° C. for 2 h and quenched by the addition of satd. aqueous NH4Cl at −78° C., then allowed to warm to RT and extracted with EtOAc. The organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude mixture was purified by silica gel chromatography on a 80 g RediSep Gold column using a 0-30% EtOAc/hexanes gradient to afford tert-butyl N-[(3S)-2-allyl-3-(fluoromethyl)-3-(2-fluoro-5-nitro-phenyl)-6,6-dimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]-N-tert-butoxycarbonyl-carbamate (2.0 g, 67%) as an off-white solid and a mixture of cis and trans (2:1) isomers. LC/MS (ESI+) m/z=610 (M+Na).

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 2 h
  2. customquenched by the addition of satd
  3. customat −78° C.
  4. temperatureto warm to RT
  5. extractionextracted with EtOAc
  6. washThe organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude mixture was purified by silica gel chromatography on a 80 g RediSep Gold column

Sources & evidence

ORD record
ord-d4e03bc5fa62403baafaeb1a2df99a6f
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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