4-(3-Chlorophenoxy)piperidine → (R)-1-[4-(3-chloro-phenoxy)-piperidin-1-yl]-3-(3-isoxazolo[5,4-b]pyridin-3-yl-phenoxy)-propan-2-ol

HRID 852182Notes

Reaction equation

HRID 852182 reaction equation
[O:1]1[CH2:3][C@@H:2]1[CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[CH:18][CH:19]=3)[O:14][N:13]=2)[CH:9]=[CH:10][CH:11]=1.[Cl:21][C:22]1[CH:23]=[C:24]([CH:32]=[CH:33][CH:34]=1)[O:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>C(O)C>[Cl:21][C:22]1[CH:23]=[C:24]([CH:32]=[CH:33][CH:34]=1)[O:25][CH:26]1[CH2:27][CH2:28][N:29]([CH2:3][C@@H:2]([OH:1])[CH2:4][O:5][C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([C:12]3[C:20]4[C:15](=[N:16][CH:17]=[CH:18][CH:19]=4)[O:14][N:13]=3)[CH:7]=2)[CH2:30][CH2:31]1

Participants

4

Reactant 2

HCID 27353174-(3-Chlorophenoxy)piperidineHCID 58928270(R)-3-(3-oxiranylmethoxy-phenyl)-isoxazolo[5,4-b]pyridine

Product 1

HCID 58928271(R)-1-[4-(3-chloro-phenoxy)-piperidin-1-yl]-3-(3-isoxazolo[5,4-b]pyridin-3-yl-phenoxy)-propan-2-olYield 50%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Dilute a 0.370 M solution (in dimethylformamide) of (R)-3-(3-oxiranylmethoxy-phenyl)-isoxazolo[5,4-b]pyridine (140 mg, 0.522 mmol) with ethanol (3.0 mL) and add solution of 4-(3-chlorophenoxy)-piperidine (121.5 mg, 0.574 mmol, 1.1 equivalents) (Table No.1, SM 7) dissolved in ethanol (0.200 M solution). Under a vented argon atmosphere, reflux the reaction mixture overnight. Concentrate the reaction mixture and purify with a Waters Sep-Pak 5 g silica gel cartridge and elute with a graded solvent mixture from 1% methanol in dichloromethane to 5% methanol in dichloromethane to give the title compound (124.6 mg, 50% Yield). Purity by LC/MS=100%, [M+H]+=480

Workup

  1. temperatureUnder a vented argon atmosphere, reflux the reaction mixture overnight
  2. concentrationConcentrate the reaction mixture
  3. custompurify with a Waters Sep-Pak 5 g silica gel cartridge
  4. washelute with a graded solvent mixture from 1% methanol in dichloromethane to 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-9c42f4fd46e04e3291b2adece2137e99
Source dataset
uspto-grants-2007_08
Patent number
US07253165B2

Reaction notes

Loading…