Methanol → (R)-((S)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethyl) 2-(6-methoxynaphthalen-2-yl)propanoate

HRID 571175Notes

Reaction equation

HRID 571175 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]([CH3:37])[C:14]([O:16][C@H:17]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=1)[CH2:18][C:19]1[C:24]([Cl:25])=[CH:23][N:22]=[CH:21][C:20]=1[Cl:26])=[O:15])[CH:7]=[CH:6]2.CO>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@@H:13]([CH3:37])[C:14]([O:16][C@H:17]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=1)[CH2:18][C:19]1[C:24]([Cl:25])=[CH:23][N:22]=[CH:21][C:20]=1[Cl:26])=[O:15])[CH:7]=[CH:6]2

Participants

4

Reactant 2

HCID 887MethanolHCID 71149994((S)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethyl) 2-(6-methoxynaphthalen-2-yl)propanoate

Product 1

HCID 71092556(R)-((S)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethyl) 2-(6-methoxynaphthalen-2-yl)propanoateYield 88%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

((S)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethyl) 2-(6-methoxynaphthalen-2-yl)propanoate (diastereoisomeric mixture prepared as described in Ex 1, Step 1, 79 g, 146 mmol) was dissolved in CHCl3 (100 ml), and MeOH (30 ml) was slowly added up to persistent opalescence and the mixture left at RT for 2 hours. The solid formed was collected by filtration and re-crystallized by CHCl3/MeOH (70 ml/20 ml) solvent system to obtain 35 g of the desired compound (yield 88%, ee 98%). Chiral HPLC analysis Rt=42.33 min; eluent:hexane:isopropanol 97:3; 1H NMR (600 MHz, CHLOROFORM-d) δ ppm 8.04 (s, 2H), 7.67 (d, J=8.79 Hz, 1H), 7.58 (d, J=8.52 Hz, 1H), 7.53 (m, 1H), 7.12-7.20 (m, 3H), 6.95 (dd, J=8.24, 1.92 Hz, 1H), 6.78-6.88 (m, 2H), 6.14 (dd, J=10.44, 4.12 Hz, 1H), 3.95 (s, 3H), 3.88 (s, 3H), 3.78-3.81 (m, 4H), 3.55 (dd, J=13.73, 10.44 Hz, 1H), 3.14 (dd, J=13.60, 4.26 Hz, 1H), 1.44 (d, J=7.14 Hz, 3H).

Workup

  1. customThe solid formed
  2. filtrationwas collected by filtration
  3. customre-crystallized by CHCl3/MeOH (70 ml/20 ml) solvent system

Sources & evidence

ORD record
ord-57a1b5bb4b0347909062d4a06d6fd635
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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