Hydrogen Peroxide → (3S,4R)-rel-tert-Butyl 3-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 714217Notes

Reaction equation

HRID 714217 reaction equation
N#N.[F:3][CH:4]1[C:9](=[CH2:10])[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]1.B1C2CCCC1CCC2.CC([O-])=[O:29].[Na+].OO>C1COCC1.O>[F:3][C@H:4]1[C@@H:9]([CH2:10][OH:29])[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]1.[F:3][C@H:4]1[C@H:9]([CH2:10][OH:29])[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]1

Participants

9

Reactant 5

HCID 784Hydrogen PeroxideHCID 947NitrogenHCID 789669-Borabicyclo(3.3.1)nonaneHCID 517045Sodium AcetateHCID 53302091Tert-butyl 3-fluoro-4-methylenepiperidine-1-carboxylate

Product 2

HCID 89875921(3S,4R)-rel-tert-Butyl 3-fluoro-4-(hydroxymethyl)piperidine-1-carboxylateHCID 90155926trans-tert-Butyl 3-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of tert-butyl 3-fluoro-4-methylenepiperidine-1-carboxylate (545 mg, 2.53 mmol) in THF (17 mL) was added dropwise a 0.5 M solution of 9-BBN (12.7 ml) at 0° C. The resulting solution was stirred for 16 h at rt. A solution of NaOAc 5M in water (1.7 mL) was added followed by H2O2 30% (1.7 mL), and the mixture was stirred for 14 h at rt. The mixture was then partitioned between EA and aq. sat. NaHCO3. The aqueous layer was extracted with EA, and the combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by FC (hexanes-EA, 3:2) to afford cis-tert-butyl 3-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate as a colorless oil and trans-tert-butyl 3-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate as a colorless oil. LC-MS-conditions 08: tR=0.65 min; [M-CH3+H]+=220.35 and tR=0.68 min; [M-CH3+H]+=220.36.

Workup

  1. stirringthe mixture was stirred for 14 h at rt
  2. customThe mixture was then partitioned between EA and aq. sat. NaHCO3
  3. extractionThe aqueous layer was extracted with EA
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by FC (hexanes-EA, 3:2)

Sources & evidence

ORD record
ord-db554a5f561541938fc5e07218534799
Source dataset
uspto-grants-2015_11
Patent number
US09187435B2

Reaction notes

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