4-Fluorophenol → N-tert-butyloxycarbonyl4-(p-fluorophenoxymethyl)piperidine
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:28]([N:35]1[CH2:40][CH2:39][CH:38]([CH2:41]O)[CH2:37][CH2:36]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:41][CH:38]2[CH2:39][CH2:40][N:35]([C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH2:36][CH2:37]2)=[CH:4][CH:3]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
4-Fluorophenol (0.52 g, 4.64 mmol) and triphenylphosphine (1.22 g, 4.64 mmol) were added to a solution of N-boc-piperidine-4-methanol (500 mg, 2.32 mmol) in anhydrous THF (12 mL) under nitrogen. The reaction mixture was cooled to 0° C. and DEAD (670 μL, 3.69 mmol) was added dropwise. The solution was allowed to warm to room temperature and stirred overnight. The reaction mixture was concentrated under reduced pressure then diluted with dichloromethane and filtered. The filtrate was washed three times with NaOH 0.2N, dried over Na2SO4 and concentrated. The residue was purified on column chromatography (eluent: pentane/EtOAc 95/5) to give the title compound (538 mg, 75%) as a yellow oil.
Workup
- temperatureto warm to room temperature
- concentrationThe reaction mixture was concentrated under reduced pressure
- additionthen diluted with dichloromethane
- filtrationfiltered
- washThe filtrate was washed three times with NaOH 0.2N
- dry with materialdried over Na2SO4
- concentrationconcentrated
- customThe residue was purified on column chromatography (eluent: pentane/EtOAc 95/5)
Sources & evidence
- ORD record
- ord-310861fd190f4c19aa3ce67a9df64b82
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09051321B2
Reaction notes
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