Isobutylene oxide → HCID 131735337, compound

HRID 627737Notes

Reaction equation

HRID 627737 reaction equation
C(OC([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]=2F)([CH3:26])[N:17]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=O)(C)(C)C.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:47][C:48]1([CH3:51])[O:50][CH2:49]1.[NH4+].[Cl-]>C1COCC1.CC(O)(C)C.CC(C)([O-])C.[K+]>[CH3:22][C:21]1([CH3:23])[S:20](=[O:25])(=[O:24])[C@@H:19]2[CH2:47][C:48]([CH3:51])([CH3:49])[O:50][C:28]3[CH:29]=[CH:30][C:31]([N+:33]([O-:35])=[O:34])=[CH:32][C:27]=3[C@@:18]2([CH3:26])[N:17]=[C:16]1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13]

Participants

8

Reactant 4

HCID 11208Isobutylene oxideHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 86728128HCID 86728128, compound

Product 1

HCID 131735337HCID 131735337, compoundYield 13.7%

Reagents, catalysts & solvents 3

HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 23665647Potassium tert-butoxideSolvent

Conditions

Temperature
-78 °C

Procedure

To a 25-mL RBF was added 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 (450 mg, 0.850 mmol) in THF (5.6 ml). The reaction solution was cooled to −78° C., then LHMDS (1.0M in THF; 2124 μl, 2.124 mmol) was added slowly. The brown solution was stirred for 15 min, then 1,1-dimethyloxirane (377 μl, 4.25 mmol) was added at −78° C. The reaction mixture was stirred from −78° C. to RT by removing dry-ice bath. 35 min later, it was quenched by 8 mL sat. aq. NH4Cl. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with satd NaCl and dried over MgSO4. The solution was filtered and concentrated to give the crude material as a brown oil. The crude mixture was dissolved in 6 ml tBuOH and potassium tert-butoxide, 1.0M solution in THF (2.5 ml, 2.55 mmol). It was stirred at RT. 20 min later, 8 mL of aq. NH4Cl was added and extracted with EtOAc. The organic extract was concentrated and was purified using 40 g Puriflash column in 20% to 35% to 50% EtOAc/Heptanes to give 56 mg of tert-butyl ((4aR,11bR)-3,3,6,6,11b-pentamethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (13% yield, less polar by TLC), and 90 mg of tert-butyl ((4aS,11bR)-3,3,6,6,11b-pentamethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (22% yield, containing impurity, more polar by TLC). MS m/z=504.0 (M+Na).

Workup

  1. stirringThe reaction mixture was stirred from −78° C. to RT
  2. customby removing dry-ice bath
  3. custom35 min later, it was quenched by 8 mL sat. aq. NH4Cl
  4. additionThe reaction mixture was diluted with water
  5. extractionextracted with EtOAc
  6. extractionThe organic extract
  7. washwas washed with satd NaCl
  8. dry with materialdried over MgSO4
  9. filtrationThe solution was filtered
  10. concentrationconcentrated
  11. customto give the crude material as a brown oil
  12. stirringIt was stirred at RT
  13. extractionextracted with EtOAc
  14. extractionThe organic extract
  15. concentrationwas concentrated
  16. customwas purified

Sources & evidence

ORD record
ord-a602178edcc4460785ecb1856c6628cb
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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