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

HRID 1798931노트

반응식

HRID 1798931 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-7c439d1ca1684e288645f75c87fb64af
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344000B2

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