Hydrogen Peroxide → HCID 97107398, compound

HRID 1507236Notes

Reaction equation

HRID 1507236 reaction equation
[BH4-].[Na+].B(F)(F)F.CC[O:9]CC.[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH:27]=2)=[CH:22][CH:21]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+].OO>C1COCC1.C(O)C.O>[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][C:23]([C@@H:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][C@H:27]2[OH:9])=[CH:22][CH:21]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

9

Reactant 5

HCID 784Hydrogen PeroxideHCID 8000Boron trifluoride etherateHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 53861764HCID 53861764, compound

Product 1

HCID 97107398HCID 97107398, compoundYield 85.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirring mixture of NaBH4 (0.93 g, 24.6 mmol) in THF (25 mL) cooled to 0° C. was added boron trifluoride etherate (3.2 mL, 25 mmol) and the mixture was allowed to warm up to rt over 1 h. It was then re-cooled to 0° C. and to it was added a solution of tert-butyl 4-(4-(benzyloxy)-phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (3 g, 8.2 mmol) in THF (10 mL). The resulting mixture was allowed to warm up to rt over 2 h. The reaction mixture was cooled again to 0° C. and H2O (10 mL), ethanol (10 mL), 10 M NaOH (10 mL) and H2O2 (8 mL, 26 mmol) were sequentially added. The final mixture was heated to 65° C. overnight. After cooling, the reaction was quenched with water and the mixture was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo yielding 2.7 g of (±)-rel-(3S,4S)-tert-butyl 4-(4-(benzyloxy)phenyl)-3-hydroxypiperidine-1-carboxylate (82% yield) as off-white solid. LCMS (method O) RT 2.41 min, m/z 382 (M−H). 1H NMR (400 MHz, DMSO-d6) δ 1.41 (s, 9H), 1.63 (m, 1H), 1.67 (m, 1H), 2.67 (m, 1H), 3.37-3.41 (m, 1H), 3.92 (m, 1H), 4.10 (m, 1H), 4.73 (d, J=2.4, 1H), 5.07 (s, 2H), 6.91 (d, J=9, 2H), 7.14 (d, J=9, 2H), 7.31-7.44 (m, 4H).

Workup

  1. temperatureto warm up to rt over 1 h
  2. temperatureIt was then re-cooled to 0° C. and to it
  3. temperatureto warm up to rt over 2 h
  4. temperatureThe reaction mixture was cooled again to 0° C.
  5. temperatureAfter cooling
  6. customthe reaction was quenched with water
  7. extractionthe mixture was extracted with ethyl acetate (2×100 mL)
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f5017c06b3d64a02875a36cb80c1ad9a
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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