Cyclohexane ethylacetate → {(3R,4S,5S)-5-[4-Nitro-3-fluoro-5-(2,2,2-trifluoro-ethoxy)-benzyl]-4-hydroxy-1,1-dioxo-hexahydro-1lambda*6*-thiopyran-3-yl}-carbamic acid tert-butyl ester

HRID 420308Notes

Reaction equation

HRID 420308 reaction equation
[C:1]([O:5][C:6](=[O:32])[NH:7][C@@H:8]1[C@@H:13]([OH:14])[C@H:12]([CH2:15][C:16]2[CH:21]=[C:20]([O:22][CH2:23][C:24]([F:27])([F:26])[F:25])[C:19]([N+:28]([O-:30])=[O:29])=[C:18]([F:31])[CH:17]=2)[CH2:11]S[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].O[O:34][S:35]([O-:37])=O.[K+].C1CCCCC1.CCOC(C)=O>C1COCC1.O>[C:1]([O:5][C:6](=[O:32])[NH:7][C@@H:8]1[C@@H:13]([OH:14])[C@H:12]([CH2:15][C:16]2[CH:21]=[C:20]([O:22][CH2:23][C:24]([F:27])([F:25])[F:26])[C:19]([N+:28]([O-:30])=[O:29])=[C:18]([F:31])[CH:17]=2)[CH2:11][S:35](=[O:37])(=[O:34])[CH2:9]1)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 21867204Cyclohexane ethylacetateHCID 23707502Potassium hydroxy sulfiteHCID 66649805HCID 66649805, compound

Product 1

HCID 131729383{(3R,4S,5S)-5-[4-Nitro-3-fluoro-5-(2,2,2-trifluoro-ethoxy)-benzyl]-4-hydroxy-1,1-dioxo-hexahydro-1lambda*6*-thiopyran-3-yl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {(3R,4S,5S)-5-[4-Nitro-3-fluoro-5-(2,2,2-trifluoro-ethoxy)-benzyl]-4-hydroxy-tetrahydro-thiopyran-3-yl}-carbamic acid tert-butyl ester (1.5 g, 3.1 mmol) in THF (20 mL) and water (12 mL) at 0° C. was added oxone (5.71 g, 9.3 mmol) in portions. After 2 h excess oxone was destroyed with sodiummetabisulfite. The reaction mixture was diluted with EtOAc (200 mL) and washed with aqueous saturated bicarbonate solution and brine. The organic phase was dried with Na2SO4, filtered and evaporated to provide a beige powder: TLC (cyclohexane-EtOAc 1:1) Rf=0.12; ESIMS [M+NH4]+=534; 1H NMR (600 MHz, DMSO-d6): δ 7.10 (m, 2H), 6.89 (d, 1H), 5.25 (d, 1H), 5.01-4.94 (m, 2H), 3.70 (m, 1H), 3.20-3.00 (m, 5H), 2.93 (m, 1H), 2.68 (m, 1H), 2.17 (m, 1H), 1.38 (s, 9H).

Workup

  1. customAfter 2 h excess oxone was destroyed with sodiummetabisulfite
  2. additionThe reaction mixture was diluted with EtOAc (200 mL)
  3. washwashed with aqueous saturated bicarbonate solution and brine
  4. dry with materialThe organic phase was dried with Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto provide a beige powder

Sources & evidence

ORD record
ord-fb536c5d9ef44c8196e36fbc1ad4b733
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

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