tert-Butyl 4-(2-(N-methoxy-N-methylcarbamoyl)-6-fluorophenyl)piperidine-1-carboxylate → Tert-butyl 4-(2-fluoro-6-formylphenyl)piperidine-1-carboxylate

HRID 1695957Notes

Reaction equation

HRID 1695957 reaction equation
CON(C)[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=1[CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1)=[O:5]>C1COCC1>[F:12][C:8]1[CH:9]=[CH:10][CH:11]=[C:6]([CH:4]=[O:5])[C:7]=1[CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1

Participants

3

Reactant 1

HCID 57774380tert-Butyl 4-(2-(N-methoxy-N-methylcarbamoyl)-6-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 57774387Tert-butyl 4-(2-fluoro-6-formylphenyl)piperidine-1-carboxylateYield 56.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Cp2Zr(H)Cl (1.45 g, 5.61 mmol, 1.5 eq.) was suspended in THF (25 mL) under N2 at room temperature in a flame-dried flask. To this suspension was added tert-butyl 4-(2-(N-methoxy-N-methylcarbamoyl)-6-fluorophenyl)piperidine-1-carboxylate (1.37 g, 3.739 mmol) in THF (50 mL). The reaction was stirred under N2 for 15 min until the mixture turned clear (monitored by TLC: no SM detected). SiO2 was then added and the mixture was concentrated and purified by ISCO flash chromatography (SiO2, 5 to 30% EtOAc in Hexanes) to give 652 mg of tert-butyl 4-(2-fluoro-6-formylphenyl)piperidine-1-carboxylate as a white solid (57% over 2 steps). LC/MS ES+1: 308.17.

Workup

  1. additionSiO2 was then added
  2. concentrationthe mixture was concentrated
  3. custompurified by ISCO flash chromatography (SiO2, 5 to 30% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-c1bdd0ec26d3463b861f520cfc70df86
Source dataset
uspto-grants-2012_04
Patent number
US08163737B2

Reaction notes

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