3-Phenoxybenzoic acid → (+/-)-2-(3-Phenoxybenzoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid ethyl ester

HRID 1983561Notes

Reaction equation

HRID 1983561 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][NH:7]1)=[O:5])[CH3:2].[O:16]([C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26](O)=[O:27])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl.CN(C)CCCN=C=NCC>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([CH:6]1[CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][N:7]1[C:26](=[O:27])[C:25]1[CH:29]=[CH:30][CH:31]=[C:23]([O:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:24]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 195393-Phenoxybenzoic acidHCID 652898Ethyl 1,2,3,4-tetrahydro-3-isoquinolinecarboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 68843784(+/-)-2-(3-Phenoxybenzoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid ethyl esterYield 99%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a stirred solution of (±)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid ethyl ester (6.26 g, 30.5 mmol) and 3-phenoxybenzoic acid (7.19 g, 33.6 mmol) in chloroform (150 mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (6.43 g, 33.5 mmol). The reaction was allowed to proceed overnight and then washed with aqueous sodium bicarbonate solution, dried (sodium sulfate) and concentrated. The crude product was purified by flash chromatography over silica (hexanes/ethyl acetate) to afford 12.07 g (99%) of product as a colorless gum. In chloroform-d solvent, the proton NMR spectra of this compound appears as a 55:45 mixture of rotamers: 1H NMR (CDCl3) δ 7.46-6.90 (m, 13H), 5.46 (t, J=5.6 Hz, 0.55H), 5.18 (d, J=17.6 Hz, 0.45H), 4.80-4.73 (m, 0.45H), 4.68-4.50 (m, 1.55H), 4.22-4.07 (m, 1.10H), 4.05-3.92 (m, 0.90H), 3.34-3.19 (m, 1.55H), 3.16-3.06 (m, 0.45H), 1.19 (t, J=7.1 Hz, 1.65H), 1.04 (t, J=7.1 Hz, 1.35H) ppm.

Workup

  1. washwashed with aqueous sodium bicarbonate solution
  2. dry with materialdried (sodium sulfate)
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography over silica (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-f2b14330249647559f96e87c826a3349
Source dataset
uspto-grants-2009_06
Patent number
US07541466B2

Reaction notes

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