Allyl bromide → HCID 86728135, compound

HRID 627674Notes

Reaction equation

HRID 627674 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]([C:27]2[CH:32]=[C:31]([N+:33]([O-:35])=[O:34])[CH:30]=[CH:29][C:28]=2[F:36])([CH3:26])[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.[K+].[CH2:47](Br)[CH:48]=[CH2:49].[NH4+].[Cl-]>C1COCC1>[CH2:49]([CH:19]1[C@:18]([C:27]2[CH:32]=[C:31]([N+:33]([O-:35])=[O:34])[CH:30]=[CH:29][C:28]=2[F:36])([CH3:26])[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]([CH3:12])([CH3:13])[CH3:14])[C:21]([CH3:23])([CH3:22])[S:20]1(=[O:25])=[O:24])[CH:48]=[CH2:47]

Participants

6

Reactant 4

HCID 7841Allyl bromideHCID 25517Ammonium ChlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86728128HCID 86728128, compound

Product 1

HCID 86728135HCID 86728135, compoundYield 94.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 3-necked RBF equipped with a mechanical stirrer, Claisen adapter with thermocouple and a nitrogen inlet was charged with tert-butyl N-tert-butoxycarbonyl-N-[(3R)-3-(2-fluoro-5-nitro-phenyl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]carbamate (8.8 g, 16.62 mmol) and THF (80 mL). The yellow solution was cooled to Tinternal−72+/−1° C. using a dry ice/IPA bath. KHMDS, 1M in THF (24.93 mL, 24.93 mmol) was added dropwise via cannula over ˜15 min keeping Tinternal<−72+/−1° C. The reaction mixture became dark brown, and was stirred at Tinternal˜−72+/−1° C. for 45 min. Allyl bromide (2.157 mL, 24.93 mmol) was added via syringe over 3 min, and stirring was continued at Tinternal<−75° C. for 75 min. 10 mL saturated aq. NH4Cl was added, the cooling bath was removed, and the reaction mixture was allowed to warm to RT. Water was added until all solids were dissolved, and the layers were separated. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified via silica gel chromatography (heptane/EtOAc: 100/0 to 40/60+5% DCM isocratic) to provide tert-butyl N-[(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 (8.93 g, 2.85:1 ratio of diastereomers) as an off-white solid. LC/MS (ESI+) m/z=592.2 (M+Na).

Workup

  1. customA 3-necked RBF equipped with a mechanical stirrer
  2. temperatureThe yellow solution was cooled to Tinternal−72+/−1° C.
  3. custom<−72+/−1° C
  4. stirringstirring
  5. waitwas continued at Tinternal<−75° C. for 75 min
  6. customthe cooling bath was removed
  7. additionWater was added until all solids
  8. dissolutionwere dissolved
  9. customthe layers were separated
  10. dry with materialThe organic layer was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude material was purified via silica gel chromatography (heptane/EtOAc: 100/0 to 40/60+5% DCM isocratic)

Sources & evidence

ORD record
ord-2b448d6727fe4f72b1ec966794265fde
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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