Ethylene Oxide → HCID 131735334, compound

HRID 627735Notes

Reaction equation

HRID 627735 reaction equation
[F:1][C@@:2]12[CH2:12][CH2:11][O:10][C:9]3[CH:13]=[CH:14][C:15]([N+:17]([O-:19])=[O:18])=[CH:16][C:8]=3[C@@:7]1([CH3:20])[N:6]=[C:5]([N:21](C(OC(C)(C)C)=O)[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:4]([CH3:37])([CH3:36])[S:3]2(=[O:39])=[O:38].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O1CC1>C1COCC1>[F:1][C@@:2]12[CH2:12][CH2:11][O:10][C:9]3[CH:13]=[CH:14][C:15]([N+:17]([O-:19])=[O:18])=[CH:16][C:8]=3[C@@:7]1([CH3:20])[N:6]=[C:5]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[C:4]([CH3:37])([CH3:36])[S:3]2(=[O:39])=[O:38]

Participants

5

Reactant 3

HCID 6354Ethylene OxideHCID 2733832Lithium HexamethyldisilazideHCID 121266513HCID 121266513, compound2×

Product 1

HCID 131735334HCID 131735334, compoundYield 40.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To an oven dried flask was added tert-butyl N-[(4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxo-5,6-dihydro-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (See procedure for Intermediate 24, Step 1) (0.260 g, 0.475 mmol) and THF (3.17 mL). The resulting mixture was cooled to −78° C. and LHMDS (1 M in THF; 0.712 mL, 0.712 mmol) was added and the mixture was stirred for 40 minutes and then oxirane (7.91 mL, 9.50 mmol) was added. The dry ice/acetone bath was removed and the mixture was stirred for 30 minutes. The resulting mixture was treated with saturated aqueous ammonium chloride and extracted with EtOAc. The organic layer was concentrated and the crude material was eluted through a silica gel column using 10-50% EtOAc/Heptane. The desired fractions were combined and concentrated down to yield tert-butyl ((4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (0.090 g, 0.191 mmol, 40.2% yield)). ESI MS: 494.1 [M+Na] and a mixture of tert-butyl ((4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate and tert-butyl N-[(4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxo-5,6-dihydro-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (89 mg, 0.156 mmol, 32.8% yield) ESI MS: 494.1/594.1 [M+Na].

Workup

  1. customTo an oven dried flask
  2. customThe dry ice/acetone bath was removed
  3. stirringthe mixture was stirred for 30 minutes
  4. additionThe resulting mixture was treated with saturated aqueous ammonium chloride
  5. extractionextracted with EtOAc
  6. concentrationThe organic layer was concentrated
  7. washthe crude material was eluted through a silica gel column
  8. concentrationconcentrated down

Sources & evidence

ORD record
ord-c6d9ad7080df4bb380b898226e18bb22
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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