Toluene → [2-(3-Methoxyphenyl)-3,4-Dihydro-6-methoxynaphthalen-1-yl][4-hydroxyphenyl]methanone

HRID 619087Notes

Reaction equation

HRID 619087 reaction equation
CCS.[Li]CCCC.[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([C:21]([C:23]1[CH:28]=[CH:27][C:26]([O:29]C)=[CH:25][CH:24]=1)=[O:22])=[C:16]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=1)[CH2:15][CH2:14]2.C1(C)C=CC=CC=1>C(OCC)C.CN(C=O)C.CCOC(C)=O>[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([C:21]([C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1)=[O:22])=[C:16]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=1)[CH2:15][CH2:14]2

Participants

8

Reactant 4

HCID 1140TolueneHCID 6343EthanethiolHCID 15434589[2-(3-Methoxyphenyl)-3,4-dihydro-6-methoxynaphthalen-1-yl][4-methoxyphenyl]methanoneHCID 178418339Butyllithium

Product 1

HCID 15458258[2-(3-Methoxyphenyl)-3,4-Dihydro-6-methoxynaphthalen-1-yl][4-hydroxyphenyl]methanone

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To EtSH (12.5 g, 14.9 mL. 0.20 mol) in anhydrous ethyl ether (300 mL) at -78° C. under a dry nitrogen atmosphere in a 1 L single neck RB flask was added slowly via syringe 1.6M n-BuLi (113 mL, 0.180 mol) over 1 hour. After addition was complete, the ether was removed under vacuum and a solution of [3,4-dihydro-6-methoxy-2-(3-methoxyphenyl)-1-naphthalenyl](4-methoxyphenyl)methanone, (24.0 g, 0.065 mol) in anhydrous DMF (150 mL) was added. The reaction mixture was heated at 70-80° C. for 2.5 hours and then at 65° C. for 20 hr. TLC analysis (SiO2, Toluene:EtOAc, 9:1) showed the starting material to be nearly gone. Two spots were present at lower Rf. These were attributed to the desired product and the corresponding diphenol (lowest spot). The reaction mixture was allowed to cool and was then poured into 500 mL iced 1N HCl solution. The crude product was extracted into EtOAc. The EtOAc phase was washed with saturated aqueous NaCl solution, dried over anhydrous MgSO4, and evaporated to a yellow oil. The product was purified by chromatography over silica gel using a gradient consisting of chloroform changing linearly to (95:5) chloroform:methanol. Following evaporation of the appropriate fractions, a yellow oil was obtained which was recrystallized from ethyl ether to yield 21.3 g, (54%) of the desired product, mp 197-8° C.

Workup

  1. additionAfter addition
  2. customthe ether was removed under vacuum

Sources & evidence

ORD record
ord-572202d6da5e4b74b24a466b74c47417
Source dataset
uspto-grants-1999_09
Patent number
US05958916

Reaction notes

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