Hydrogen Peroxide → HCID 118207459, compound

HRID 1507275Notes

Reaction equation

HRID 1507275 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][C:21]=1[F:39])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+].OO>C1COCC1.CCO>[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]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:28][C@@H:27]2[OH:9])=[CH:22][C:21]=1[F:39])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

8

Reactant 5

HCID 784Hydrogen PeroxideHCID 8000Boron trifluoride etherateHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 118207545HCID 118207545, compound

Product 1

HCID 118207459HCID 118207459, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To sodium borohydride (2.282 g, 60.3 mmol) in THF (81 ml) at 0° C. was added boron trifluoride diethyl etherate (9.86 ml, 78 mmol) dropwise via addition funnel. The ice bath was removed and the solution was allowed to warm to rt and stir for 1 h. The reaction was chilled to 0° C., then tert-butyl 4-(4-(benzyloxy)-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate (7.46 g, 19.5 mmol) in THF (8.11 ml) was added dropwise via additional funnel. After complete additional, the reaction was allowed to warm to rt and was stirred for 2 h. The reaction was cooled to 0° C. and quenched with water (16.2 ml) until the effervescence subsided. To this mixture was sequentially added aqueous 10% sodium hydroxide (14.2 ml, 38.9 mmol), aqueous 30% hydrogen peroxide (13.91 ml, 136 mmol) and EtOH (16.2 ml). The resulting mixture was stirred at rt for 16 h. The mixture was diluted with ice water and extracted with dichloromethane. The combined organic layers were dried with magnesium sulfate, filtered, and concentrated in vacuo to afford (±)-rel-(3R,4R)-tert-butyl 4-(4-(benzyloxy)-3-fluorophenyl)-3-hydroxypiperidine-1-carboxylate (7.32 g, 94% yield) as a white solid: LC-MS [M+H]+=328.2; 1H NMR (500 MHz, DMSO-d6) δ 7.53-7.28 (m, 5H), 7.18-7.07 (m, 2H), 6.97 (d, J=8.2 Hz, 1H), 5.14 (s, 2H), 4.82 (d, J=5.6 Hz, 1H), 4.10 (br. s., 1H), 3.95 (br. s., 1H), 3.40 (tt, J=10.2, 5.2 Hz, 1H), 2.81-2.60 (m, 1H), 2.46-2.35 (m, 1H), 1.66 (dd, J=13.4, 3.1 Hz, 1H), 1.59-1.46 (m, 1H), 1.42 (s, 9H).

Workup

  1. additiondropwise via addition funnel
  2. customThe ice bath was removed
  3. temperatureThe reaction was chilled to 0° C.
  4. temperatureto warm to rt
  5. stirringwas stirred for 2 h
  6. temperatureThe reaction was cooled to 0° C.
  7. customquenched with water (16.2 ml) until the effervescence
  8. stirringThe resulting mixture was stirred at rt for 16 h
  9. extractionextracted with dichloromethane
  10. dry with materialThe combined organic layers were dried with magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a0c39f8f356b458d8c037c20fc06b778
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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