Toluene → (S)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethanol

HRID 571176Notes

Reaction equation

HRID 571176 reaction equation
COC1C=C2C(=CC=1)C=C([C@@H](C)C([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)C=C2.C1(C)C=CC=CC=1.CC(C)([O-])C.[K+]>CO.O>[Cl:25][C:24]1[CH:23]=[N:22][CH:21]=[C:20]([Cl:26])[C:19]=1[CH2:18][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)[OH:16]

Participants

6

Reactant 3

HCID 1140TolueneHCID 23665647Potassium tert-butoxideHCID 71092556(R)-((S)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethyl) 2-(6-methoxynaphthalen-2-yl)propanoate

Product 1

HCID 71092454(S)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethanol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

(R)—((S)-2-(3,5-dichloropyridin-4-yl)-1-(3,4-dimethoxyphenyl)ethyl) 2-(6-methoxynaphthalen-2-yl)propanoate (30 g, 56 mmol) was dissolved in MeOH, and toluene was slowly added. Potassium terbutoxide was slowly added to the suspension. The mixture was stirred for 24 hours at RT. The reaction was diluted with water (500 ml), and the aqueous mixture was extracted with CHCl3 (500 ml). The organic layer was dried over Na2SO4 and the solvent was evaporated under vacuum. The residue was crystallized from CHCl3 (100 ml) and hexane (20 ml). The mother liquor was concentrated and recrystallized with an analogous procedure giving a second crop of desired compound. In total, 16 g of the title compound (87% yield) were obtained. Chiral HPLC analysis Rt=58.03 min; eluent:hexane:isopropanol=95:5; [α]D20=+10.21 (c=0.506, Methanol); 1H NMR (400 MHz, acetone) δ ppm 8.47 (s, 2H), 6.96-7.15 (m, 1H), 6.87 (m, 2H), 4.93-5.21 (m, 1H), 4.50 (d, J=3.97 Hz, 1H), 3.78 (s, 6H), 3.44 (dd, J=12.79, 8.38 Hz, 1H), 3.22 (dd, J=13.01, 5.51 Hz, 1H). MS/ESI+ [MH]+: 328.19

Workup

  1. extractionthe aqueous mixture was extracted with CHCl3 (500 ml)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customthe solvent was evaporated under vacuum
  4. customThe residue was crystallized from CHCl3 (100 ml) and hexane (20 ml)
  5. concentrationThe mother liquor was concentrated
  6. customrecrystallized with an analogous procedure

Sources & evidence

ORD record
ord-385745f1bbc542a2953e03498f4a61a6
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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