Piperidine → HCID 20066012, compound

HRID 359060Notes

Reaction equation

HRID 359060 reaction equation
[CH2:1]([N:8]([CH2:20][CH2:21][C:22]1[CH:33]=[CH:32][C:25]([O:26][CH2:27][C:28](OC)=[O:29])=[CH:24][CH:23]=1)[CH2:9][CH:10]([OH:19])[CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>CO>[CH2:1]([N:8]([CH2:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([O:26][CH2:27][C:28]([N:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)=[O:29])=[CH:32][CH:33]=1)[CH2:9][CH:10]([OH:19])[CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 8082PiperidineHCID 20065995HCID 20065995, compound

Product 1

HCID 20066012HCID 20066012, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl 4-[2-(N-benzyl-N-(2-hydroxy-3-phenoxypropyl)amino)ethyl]phenoxyacetate (6.0 g) and piperidine (16 ml) in methanol (60 ml) was stored at room temperature for 4 days. The solvent and excess reagent were evaporated under reduced pressure. Toluene was added to the residue and volatile material was evaporated. This procedure was repeated twice more. The crude intermediate (8.0 g) was purified by chromatography on K60 silica (210 g) using a mixture of methanol and dichloromethane of increasing polarity (1% to 2% methanol) to give N-(4-[2-(N-benzyl-N-(2-hydroxy-3-phenoxypropyl)amino)ethyl]phenoxyacetyl)piperidine (6.2 g) as a gum. The purified intermediate (6.2 g) was debenzylated in an analogous manner to that of Example 23, to give a colourless solid (5.1 g) which was recrystallised from propan 2-ol to yield N-(4-[2-(2-hydroxy-3-phenoxypropylamino)ethyl]phenoxyacetyl)piperidine hydrochloride (3.7 g) m.p. 139°-41°; NMR: 1.40-1.70 [m,6H, CH2 (CH2)3CH2 ]; 2.90-3.10[m,2H, CH2C6H4 ]; 3.10-3.35[m,4H, CH2NHCH2 ]; 3.35-3.55[m,4H, CH2NCH2 ]; 4.03[m,2H,PhOCH2 ]; 4.30[m,1H,CHOH]; 4.75[s,2H, OCH2CO]; 6.85-7.05[m,5H, aromatic H]; 7.15-7.38[m,4H, aromatic H]: microanalysis: found: C, 64.2; H, 7.4; N, 5.8; Cl, 7.7%; C24H32N2O4.HC1 requires: C, 64.2; H, 7.4; N, 6.2; Cl 7.9%.

Workup

  1. customThe solvent and excess reagent were evaporated under reduced pressure
  2. additionToluene was added to the residue and volatile material
  3. customwas evaporated
  4. customThe crude intermediate (8.0 g) was purified by chromatography on K60 silica (210 g)
  5. additiona mixture of methanol and dichloromethane
  6. temperatureof increasing polarity (1% to 2% methanol)

Sources & evidence

ORD record
ord-18dc603cbbac4a90b1ec47b4bd353b0b
Source dataset
uspto-grants-1991_03
Patent number
US04999377

Reaction notes

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