Hydrogen Peroxide → HCID 131729391, compound

HRID 420335Notes

Reaction equation

HRID 420335 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([C@H:11]([NH:13][C@@H:14]2[C@@H:19]([OH:20])[C@H:18]([CH2:21][C:22]3[CH:27]=[C:26]([O:28][C@H:29]([CH2:34][O:35][CH3:36])[C:30]([F:33])([F:32])[F:31])[C:25]([N+:37]([O-:39])=[O:38])=[C:24]([F:40])[CH:23]=3)[CH2:17][S:16][CH2:15]2)[CH3:12])[CH:8]=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[OH:41]O>C1COCC1.CC(O)=O.CCOC(C)=O>[C:1]([C:5]1[CH:6]=[C:7]([C@H:11]([NH:13][C@@H:14]2[C@@H:19]([OH:20])[C@H:18]([CH2:21][C:22]3[CH:27]=[C:26]([O:28][C@H:29]([CH2:34][O:35][CH3:36])[C:30]([F:32])([F:31])[F:33])[C:25]([N+:37]([O-:39])=[O:38])=[C:24]([F:40])[CH:23]=3)[CH2:17][S:16](=[O:41])[CH2:15]2)[CH3:12])[CH:8]=[CH:9][CH:10]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 2

HCID 784Hydrogen PeroxideHCID 66649551HCID 66649551, compound

Product 1

HCID 131729391HCID 131729391, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (3R,4S,5S)-3-[(R)-1-(3-tert-butyl-phenyl)-ethylamino]-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxymethyl-ethoxy)-benzyl]-tetrahydro-thiopyran-4-ol (0.249 g, 0.423 mmol) in THF (2 mL) and AcOH (1 mL) was treated with 0.22 mL 30% H2O2 and stirred for 18 h at 25° C. The mixture was diluted with EtOAc and washed with aq. Na2S2O3, and brine. The organic layer was dried over Na2SO4 and evaporated to give (3R,4S,5S)-3-[(R)-1-(3-tert-butyl-phenyl)-ethylamino]-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxymethyl-ethoxy)-benzyl]-1-oxo-hexahydro-1lambda*4*-thiopyran-4-ol as a mixture of sulfoxide diastereomers (HPLC RtH1=2.30, 2.39 min; ESIMS [M+H]+=605), pure enough for further transformation. This product was dissolved in THF-MeOH 4:1 (5 mL) and stirred in the presence of 10% Pd—C (0.1 g) under an atmosphere of hydrogen at 45° C. for 1.5 h. The mixture was filtered over Celite, evaporated and dissolved in 5 mL 3N HCl in MeOH. After 3 d the reaction mixture was concentrated and taken up in 10% aq. Na2CO3 solution and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4, filtered and evaporated. The title compound was obtained after purification by column chromatography on silica gel (EtOAc/5% MeOH) 70-0% hexane as a colorless foam: HPLC RtH1=2.535 min; ESIMS [M+H]+=575; [α]D=−9.8° (c=0.4, CH2Cl2); 1H NMR (600 MHz, DMSO-d6): δ 7.37 (s, 1H), 7.23-7.20 (m, 2H), 7.13 (m, 1H), 6.69 (s, 1H), 6.61 (d, 1H), 5.10 (m, 1H), 4.82 (s, OH), 4.59-4.55 (NH2), 3.80 (m, 1H), 3.70 (m, 2H), 3.30 (s, 3H), 3.23 (d, 1H), 3.02 (m, 1H), 2.92 (m, 1H), 2.80 (m, 1H), 2.62 (m, 1H), 2.39 (m, 1H), 2.25-2.18 (m, 3H), 1.25 (s, 9H), 1.20 (d, 3H).

Workup

  1. washwashed with aq. Na2S2O3, and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customevaporated

Sources & evidence

ORD record
ord-49f1cc45a9f84410b4f6e57d6199938a
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

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