Selectfluor → Benzyl 3-fluoro-4-oxopiperidine-1-carboxylate

HRID 1971949Notes

Reaction equation

HRID 1971949 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH:15]=[C:14]([O:17][Si](C)(C)C)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[B-](F)(F)(F)[F:23].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(#N)C.C(O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH:13]([F:23])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 2724933SelectfluorHCID 57502431Benzyl 4-((trimethylsilyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 42609253Benzyl 3-fluoro-4-oxopiperidine-1-carboxylateYield 12.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 4-trimethylsilanyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid benzyl ester (5 g, 16.4 mmol) in acetonitrile at 0° C. was added 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate (6.4 g, 18 mmol). The solution was stirred overnight at room temperature, concentrated, diluted with EtOAc and washed with water. The organics were dried over sodium sulfate, filtered, concentrated, and purified by column chromatography using 40-60% EtOAc in hexanes to give 3-fluoro-4-oxo-piperidine-1-carboxylic acid benzyl ester (3.1 g) To a stirred solution of 3-fluoro-4-oxo-piperidine-1-carboxylic acid benzyl ester (500 mg, 2 mmol) in ethanol (6 mL) was added sodium borohydride (100 mg, 2.6 mmol). After 0.5 hr, the mixture was concentrated, diluted with EtOAc and washed with water. The organics were dried over sodium sulfate, filtered, concentrated, and purified by column chromatography using 40-70% EtOAc in hexanes to give (±)-trans-3-fluoro-4-hydroxy-piperidine-1-carboxylic acid benzyl ester (120 mg).

Workup

  1. concentrationconcentrated
  2. additiondiluted with EtOAc
  3. washwashed with water
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-2f23163b51f2419eb763b0b36bc43910
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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