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

HRID 1021224ノート

反応式

HRID 1021224 の反応式
[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]

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
55 °C

実験手順

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 1.9 M DIAD/toluene solution (0.5 ml) was added dropwise to the reaction mixture, followed by stirring at 55° C. overnight. Then, a 1 M 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 1 M 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).

後処理

  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 1 M 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)

出典と根拠

ORDレコード
ord-ade52adf39d641179137a31e51c9a610
出典データセット
uspto-grants-2014_05
特許番号
US08716470B2

反応ノート

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