Ammonium Chloride → HCID 131735328, compound

HRID 627658Notes

Reaction equation

HRID 627658 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.[O:47]1[C@H:49]([CH3:50])[CH2:48]1.[NH4+].[Cl-]>CC(O)(C)C.CC(C)([O-])C.[K+].C1COCC1>[CH3:23][C:21]1([CH3:22])[S:20](=[O:25])(=[O:24])[C@@H:19]2[CH2:48][C@@H:49]([CH3:50])[O:47][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[CH2:48][C@@H:49]([CH3:50])[O:47][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 146261(R)-1,2-EpoxypropaneHCID 2733832Lithium HexamethyldisilazideHCID 86728128HCID 86728128, compound

Product 2

HCID 131735328HCID 131735328, compoundYield 28.3%HCID 131735329HCID 131735329, compoundYield 15.29%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
-78 °C

Procedure

To a 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 (200 mg, 0.378 mmol) and dry THF (2.5 ml). The reaction mixture was cooled to −78° C. and LHMDS (1 M in THF; 0.94 ml, 0.944 mmol) was added. The mixture was stirred fort 0 min and then (r)-(+)-1,2-epoxypropane (53 μl, 0.755 mmol) was added. The reaction mixture was stirred for 1 hr at −78° C. and then dry ice/acetone bath was removed. The mixture was allowed to warm up to RT and stirred for 1 h. It was quenched by 3 ml of 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 2 ml tBuOH and potassium tert-butoxide, 1.0 M solution THF (1.1 ml, 1.1 mmol). It was stirred at RT. 20 min later, 5 mL of sat. aq. NH4Cl was added and it was extracted with EtOAc. It was concentrated and was purified by silica gel chromatography eluting with 20% to 35% to 50% EtOAc in heptane to give tert-butyl ((4aR,6R,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 (50 mg, 0.107 mmol, 28.3% yield) and tert-butyl ((4aS,6R,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 (27 mg, 0.058 mmol, 15.29% yield). MS m/z=490.0 (M+23).

Workup

  1. stirringThe reaction mixture was stirred for 1 hr at −78° C.
  2. customdry ice/acetone bath was removed
  3. temperatureto warm up to RT
  4. stirringstirred for 1 h
  5. customIt was quenched by 3 ml of sat. aq
  6. additionThe reaction mixture was diluted with water
  7. extractionextracted with EtOAc
  8. extractionThe organic extract
  9. washwas washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationThe solution was filtered
  12. concentrationconcentrated
  13. customto give the crude material as a brown oil
  14. stirringIt was stirred at RT
  15. extractionit was extracted with EtOAc
  16. concentrationIt was concentrated
  17. customwas purified by silica gel chromatography
  18. washeluting with 20% to 35% to 50% EtOAc in heptane

Sources & evidence

ORD record
ord-f52e0b391d5149ee916861578ec96bce
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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