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

HRID 272866Notes

Reaction equation

HRID 272866 reaction equation
[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

Participants

5

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-205b305c4e9f4674b96ac2e056a4d247
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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