Allyl bromide → HCID 86728116, compound

HRID 627649Notes

Reaction equation

HRID 627649 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@:9]2([CH3:27])[CH2:14][S:13](=[O:16])(=[O:15])[C:12]([CH3:18])([CH3:17])[C:11]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[N:10]2)[C:5]([F:8])=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:38](Br)[CH:39]=[CH2:40]>C1COCC1>[CH2:40]([C@H:14]1[S:13](=[O:15])(=[O:16])[C:12]([CH3:18])([CH3:17])[C:11]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[N:10][C@@:9]1([C:4]1[C:5]([F:8])=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=1)[CH3:27])[CH:39]=[CH2:38]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86728115HCID 86728115, compound

Product 1

HCID 86728116HCID 86728116, compoundYield 63.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (R)-tert-butyl (5-(5-bromo-2-fluoropyridin-3-yl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (1.02 g, 2.197 mmol) in THF (13 mL) at −78° C. was added potassium bis(trimethylsilyl)amide (1 M in THF, 13.2 mL, 13.2 mmol) dropwise. The solution was stirred at −78° C. for 30 min and allyl bromide (0.570 mL, 6.59 mmol) was added. The reaction mixture was stirred at −78° C. for 70 min, quenched with saturated NH4Cl, warmed to room temperature and diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (2×). The combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, concentrated. Purification by flash column chromatography on silica gel (40 g, 10% to 40% EtOAc in hexanes) gave tert-butyl ((5R,6R)-6-allyl-5-(5-bromo-2-fluoropyridin-3-yl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (0.703 g, 1.39 mmol, 63% yield) as a white solid, LC/MS (ESI+) m/z=504 (M+H); and tert-butyl ((5R,6S)-6-allyl-5-(5-bromo-2-fluoropyridin-3-yl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (0.280 g, 0.555 mmol, 25% yield) as white solid, LC/MS (ESI+) m/z=504 (M+H). The two products were recombined and used in the next step.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 70 min
  2. customquenched with saturated NH4Cl
  3. temperaturewarmed to room temperature
  4. additiondiluted with EtOAc and water
  5. extractionThe aqueous phase was extracted with EtOAc (2×)
  6. washThe combined organic extracts were washed with brine (1×)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash column chromatography on silica gel (40 g, 10% to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-7084b568302e4bd6be0cc80d9feaaea5
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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