Acetic Acid → 2-Fluoro-4-methyl-6-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}phenol

HRID 1798931ノート

反応式

HRID 1798931 の反応式
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([NH2:9])[C:3]=1[OH:10].[CH3:11][C:12]1([N:18]2[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]2)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C([BH3-])#N.C(O)(=O)C>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([NH:9][CH:21]2[CH2:22][CH2:23][N:18]([C:12]3([CH3:11])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[CH2:19][CH2:20]2)[C:3]=1[OH:10]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 552821212-Amino-6-fluoro-4-methylphenolHCID 596832511-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinone

生成物 1

HCID 582873142-Fluoro-4-methyl-6-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}phenol収率 46.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

2-Amino-6-fluoro-4-methylphenol (D16, 49 mg, 0.34 mmol) was dissolved in DCM (3 mL) and 1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinone (D12, 68 mg, 0.34 mmol), polymer supported cyanoborohydride (160 mg, 0.69 mmol, 4.3 mmol/g) and acetic acid (0.10 mL, 1.72 mmol) were all added at room temperature. The mixture was reacted at 100° C. in the microwave for 10 min. The mixture was then cooled to room temperature, filtered and the solvent was removed under vacuum to give the crude product, an orange oil, which was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM) to give 2-fluoro-4-methyl-6-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}phenol (D17, 51 mg, 42%) as a white solid.

後処理

  1. additionall added at room temperature
  2. customThe mixture was reacted at 100° C. in the microwave for 10 min
  3. filtrationfiltered
  4. customthe solvent was removed under vacuum
  5. customto give the crude product
  6. customan orange oil, which was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM)

出典と根拠

ORDレコード
ord-7c439d1ca1684e288645f75c87fb64af
出典データセット
uspto-grants-2013_01
特許番号
US08344000B2

反応ノート

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