Nitrogen → Tert-butyl 3-fluoro-4-methylenepiperidine-1-carboxylate

HRID 714218Notes

Reaction equation

HRID 714218 reaction equation
N#N.[CH3:3]C(C)([O-])C.[K+].[F:9][CH:10]1[C:15](=O)[CH2:14][CH2:13][N:12]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:11]1.OS([O-])=O.[Na+]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[F:9][CH:10]1[C:15](=[CH2:3])[CH2:14][CH2:13][N:12]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:11]1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10560711TERT-BUTYL 3-FLUORO-4-OXOPIPERIDINE-1-CARBOXYLATEHCID 23665647Potassium tert-butoxideHCID 23665763Sodium Bisulfite

Product 1

HCID 53302091Tert-butyl 3-fluoro-4-methylenepiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a suspension of methyltriphenylphosphonium bromide (1.68 g, 4.60 mmol) in dry THF (30 mL) was added potassium tert-butoxide (544 mg, 4.60 mmol) at rt. The reaction mixture was stirred at rt for 30 min. A solution of tert-butyl 3-fluoro-4-oxopiperidine-1-carboxylate (500 mg, 2.30 mmol) in dry THF (10 mL) was then added and the resulting suspension stirred at rt for 16 h. Aq. 10% NaHSO3 was then added, the mixture extracted with EA. The org. layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by FC (hexanes-EA, 19:1) to afford the title compound as a colorless oil. LC-MS-conditions 08: tR=0.84 min; [M-CH3+H]+=201.33.

Workup

  1. stirringthe resulting suspension stirred at rt for 16 h
  2. extractionthe mixture extracted with EA
  3. dry with materiallayer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by FC (hexanes-EA, 19:1)

Sources & evidence

ORD record
ord-ed765292c8b94f17ad071a5cd6208b31
Source dataset
uspto-grants-2015_11
Patent number
US09187435B2

Reaction notes

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