Ammonium Chloride → HCID 131735332, compound

HRID 627668Notes

Reaction equation

HRID 627668 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]=2F)([CH3:26])[N:17]=1)C(=O)OC(C)(C)C)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:47][C@H:48]1[CH2:50][O:49]1.[NH4+].[Cl-]>C1COCC1.CC(O)(C)C.CC(C)([O-])C.[K+]>[CH3:23][C:21]1([CH3:22])[S:20](=[O:25])(=[O:24])[C@@H:19]2[CH2:47][C@H:48]([CH3:50])[O:49][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:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2].[CH3:23][C:21]1([CH3:22])[S:20](=[O:25])(=[O:24])[C@H:19]2[CH2:47][C@H:48]([CH3:50])[O:49][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:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2]

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 146262(2S)-2-MethyloxiraneHCID 2733832Lithium HexamethyldisilazideHCID 86728128HCID 86728128, compound

Product 2

HCID 131735332HCID 131735332, compoundHCID 131735333HCID 131735333, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
-78 °C

Procedure

To a 25-mL round-bottomed dry flask 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 (420 mg, 0.793 mmol) in THF (5 ml). The reaction solution was cooled to −78° C., then LHMDS (1 M in THF; 2.0 ml, 2.0 mmol) was added slowly. It was stirred for 20 min, then (S)-2-methyloxirane (92 μl, 1.586 mmol) was added at −78° C. The reaction mixture was stirred from −78° C. to 0° C. After 15 min, it was quenched by sat. aq. NH4Cl. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with brine 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 4 ml tBuOH and potassium tert-butoxide, 1.0M solution in THF (2.4 ml, 2.4 mmol) was added. It was stirred at RT. 50 min later, 5 ml of sat. NH4Cl was added and the reaction mixture was extracted with EtOAc. It was concentrated and was purified by silica gel chromatography using 20% to 35% to 50% EtOAc/heptane to give 70 mg of tert-butyl ((4aR,6S,11bR)-3,3,6,11b-tetramethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (less polar peak by TLC) and 50 mg of tert-butyl ((4aS,6S,11bR)-3,3,6,11b-tetramethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (more polar peak by TLC). MS m/z=490.2 (M+23).

Workup

  1. stirringThe reaction mixture was stirred from −78° C. to 0° C
  2. waitAfter 15 min
  3. customit was quenched by sat. aq. NH4Cl
  4. additionThe reaction mixture was diluted with water
  5. extractionextracted with EtOAc
  6. extractionThe organic extract
  7. washwas washed with brine
  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. extractionthe reaction mixture was extracted with EtOAc
  14. concentrationIt was concentrated
  15. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-e4c786517e184409aecf289aaf801a89
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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