Triphenylphosphine → {2-Fluoro-3-[4-(pyridin-4-yloxy)piperidin-1-yl]phenyl}methanol

HRID 2171624Notes

Reaction equation

HRID 2171624 reaction equation
[Si]([O:8][CH2:9][C:10]1[C:11]([F:23])=[C:12]([N:16]2[CH2:21][CH2:20][CH:19]([OH:22])[CH2:18][CH2:17]2)[CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.[N:24]1[CH:29]=[CH:28][C:27](O)=[CH:26][CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(C)C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C1COCC1>[F:23][C:11]1[C:12]([N:16]2[CH2:17][CH2:18][CH:19]([O:22][C:27]3[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=3)[CH2:20][CH2:21]2)=[CH:13][CH:14]=[CH:15][C:10]=1[CH2:9][OH:8]

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 11078149TBAF tetrahydrofuranHCID 866862001-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]piperidin-4-olHCID 178418642HCID 178418642, compoundHCID 178459888HCID 178459888, compound

Product 1

HCID 68310417{2-Fluoro-3-[4-(pyridin-4-yloxy)piperidin-1-yl]phenyl}methanolYield 47.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

1-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]piperidin-4-ol (200 mg) and pyridin-4-ol (65 mg) were mixed with THF (3 ml), and triphenylphosphine (250 mg) was added thereto. A 1.9M DIAD/toluene solution (0.5 ml) was added dropwise to the reaction mixture, followed by stirring at 55° C. overnight. Then, a 1M TBAF/THF solution (1 ml) was added to the reaction mixture, followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and diethyl ether and 1M hydrochloric acid were added thereto. The organic layer was separated by a liquid separation operation, and the aqueous layer was washed with diethyl ether twice again. The aqueous layer was adjusted to a pH of around 10 by the addition of a 4 M aqueous NaOH solution, and extracted with CHCl3. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH) to obtain {2-fluoro-3-[4-(pyridin-4-yloxy)piperidin-1-yl]phenyl}methanol (84 mg).

Workup

  1. additionwas added
  2. stirringby stirring at room temperature for 1 hour
  3. concentrationThe reaction mixture was concentrated under reduced pressure, and diethyl ether and 1M hydrochloric acid
  4. additionwere added
  5. customThe organic layer was separated by a liquid separation operation
  6. washthe aqueous layer was washed with diethyl ether twice again
  7. additionThe aqueous layer was adjusted to a pH of around 10 by the addition of a 4 M aqueous NaOH solution
  8. extractionextracted with CHCl3
  9. dry with materialThe organic layer was dried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-e3a3d733903a437daccfd7950466b8dd
Source dataset
uspto-grants-2015_06
Patent number
US09051283B2

Reaction notes

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