Piperidin-4-ol → 1-{4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-ylmethyl}piperidin-4-ol

HRID 272866노트

반응식

HRID 272866 반응식
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH:22]=O)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:24][CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][N:28]4[CH2:29][CH2:30][CH:25]([OH:24])[CH2:26][CH2:27]4)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[CH:12][CH:11]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

참가 물질

5

반응물 2

HCID 79341Piperidin-4-olHCID 598374274-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde

생성물 1

HCID 598373811-{4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-ylmethyl}piperidin-4-ol수율 73%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매HCID 702Ethanol용매

실험 절차

4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde (420 mg, 1.30 mmol, 1 wt), 4-hydroxypiperidine (268 mg, 2.60 mmol), absolute ethanol (17 ml, 40 vol), activated 3 Å molecular sieves (420 mg), titanium (IV) isopropoxide (1.94 ml, 4.62 vol) and STAB (2.34 g, 11.1 mmol) was reacted in accordance with the general procedure D. The isolated waxy solid was purified by preparative HPLC, eluting with acetonitrile/water/0.1% TFA as a gradient, to give the title compound as a white solid (380 mg, 73%). 1H NMR (400 MHz, CDCl3) δ7.21 (d, 2H), 6.86 (d, 2H), 4.02 (t, 2H), 3.75 (dt, 2H), 3.59-3.47 (m, 2H), 2.63 (t, 2H), 2.53 (br s, 4H), 2.35 (s, 2H), 2.33-2.25 (m, 2H), 2.13-1.96 (m, 6H), 1.93-1.83 (m, 2H), 1.82-1.76 (m, 4H), 1.72-1.59 (m, 3H), 1.47-1.29 (m, 3H).

후처리

  1. customThe isolated waxy solid was purified by preparative HPLC
  2. washeluting with acetonitrile/water/0.1% TFA as a gradient

출처 및 근거

ORD 기록
ord-205b305c4e9f4674b96ac2e056a4d247
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07456164B2

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