Hydrogen Peroxide → HCID 178453568, compound

HRID 2389116Notes

Reaction equation

HRID 2389116 reaction equation
[CH:1]1([C@H:7]2[CH2:12][CH2:11][C@H:10]([O:13][C:14]3[C:15]([C:36]([F:39])([F:38])[F:37])=[C:16]4[C:21](=[CH:22][CH:23]=3)[CH:20]=[C:19]([C@:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:27])[CH2:25][OH:26])[CH:18]=[CH:17]4)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)[P:43]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])C.N1C=NN=N1.[O:61]1CCCC1.OO.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>>[CH:1]1([C@H:7]2[CH2:12][CH2:11][C@H:10]([O:13][C:14]3[C:15]([C:36]([F:37])([F:38])[F:39])=[C:16]4[C:21](=[CH:22][CH:23]=3)[CH:20]=[C:19]([C@:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:34])[CH3:32])([CH3:27])[CH2:25][O:26][P:43]([O:44][C:45]([CH3:46])([CH3:47])[CH3:48])([O:49][C:50]([CH3:51])([CH3:52])[CH3:53])=[O:61])[CH:18]=[CH:17]4)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 7

HCID 784Hydrogen PeroxideHCID 962WaterHCID 8028TetrahydrofuranHCID 24477Sodium ThiosulfateHCID 4251849Di-tert-butyl diethylphosphoramiditeHCID 178418441HCID 178418441, compoundHCID 178453524HCID 178453524, compound

Product 1

HCID 178453568HCID 178453568, compoundYield 80%

Conditions

Temperature
23 °C

Procedure

tert-Butyl (R)-2-(6-(trans-4-cyclohexylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)-1-hydroxypropan-2-ylcarbamate was then treated with di-tert-butyl N,N-diethylphosphoramidite (66.6 mg, 0.000267 mol) and 1H-tetrazole (23.4 mg, 0.000334 mol) in tetrahydrofuran (2 mL, 0.03 mol) at 23° C. for 8 hours. 9 M of hydrogen peroxide in water (0.0296 mL, 0.000267 mol) was added to the reaction mixture at −20° C., and the reaction mixture was then stirred for 1 hour at 23° C., followed by sodium thiosulfate (52.8 mg, 0.000334 mol) at −30° C. All the excess of solvents were removed, and the residue was purified via chromatography (SiO2, 4 g, 0-35% ethyl acetate/hexanes) to give a pure intermediate (30.3 mg, 80%). 1H NMR (MeOD) δ: 8.11 (d, J=9.3 Hz, 1H), 8.02 (d, J=9.0 Hz, 1H), 7.84 (d, J=1.8 Hz, 1H), 7.62 (dd, J=9.2, 1.9 Hz, 1H), 7.46 (d, J=9.3 Hz, 1H), 4.38-4.49 (m, 1H), 4.34 (br. s., 1H), 4.25-4.31 (m, 1H), 2.17 (d, J=11.3 Hz, 2H), 1.85 (d, J=10.5 Hz, 2H), 1.70-1.79 (m, 6H), 1.60-1.69 (m, 1H), 1.51 (m, 13H), 1.41-1.47 (m, 23H), 0.97-1.32 (m, 2H)

Workup

  1. customAll the excess of solvents were removed
  2. customthe residue was purified via chromatography (SiO2, 4 g, 0-35% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1c7f49db32ab4a9aae5e2ab5eed21510
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

Loading…