Tetrahydrofuran → Ethyl 4-[1-(2,2-dimethoxyethyl)-2-{1(tol-4-yl)3,4-dihydro-4,4-dimethyl-naphthalen-7-yl}-(E)-ethenyl]-benzoate

HRID 1375280Notes

Reaction equation

HRID 1375280 reaction equation
C(OP([C:9]([O:25][CH3:26])([O:23][CH3:24])[CH2:10][CH2:11][C:12]1[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][CH:13]=1)(OCC)=O)C.C([N-][CH:31]([CH3:33])[CH3:32])(C)C.[Li+].C[C:36]1(C)[CH:45]=[C:44]([C:46]2S[C:49]([CH3:51])=[CH:48][CH:47]=2)[C:43]2[C:38](=[CH:39][CH:40]=[C:41]([CH:52]=O)[CH:42]=2)S1.[CH2:55]1COC[CH2:56]1>>[CH3:26][O:25][CH:9]([O:23][CH3:24])[CH2:10]/[C:11](/[C:12]1[CH:13]=[CH:14][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:21][CH:22]=1)=[CH:52]\[C:41]1[CH:42]=[C:43]2[C:38]([C:31]([CH3:32])([CH3:33])[CH2:36][CH:45]=[C:44]2[C:46]2[CH:47]=[CH:48][C:49]([CH3:51])=[CH:56][CH:55]=2)=[CH:39][CH:40]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 2724682Lithium diisopropylamideHCID 57037360Ethyl 4-(diethoxyphosphoryl-3,3-dimethoxypropyl)benzoate2×HCID 1317205772,2-Dimethyl-4(2-methyl-thien-5-yl)-thiochrom-3-en-6-al2×

Product 1

HCID 86588679Ethyl 4-[1-(2,2-dimethoxyethyl)-2-{1(tol-4-yl)3,4-dihydro-4,4-dimethyl-naphthalen-7-yl}-(E)-ethenyl]-benzoate

Conditions

Temperature
-5 °C

Procedure

To a cold (−78° C.) solution of ethyl 4-(diethoxyphosphoryl-3,3-dimethoxypropyl)benzoate (Compound D, 500 mg, 1.29 mmol) in THF (2.5 mL) was added freshly prepared lithium diisopropylamide in THF(1.5 mmol). The mixture was allowed to warm to −5° C. over a period of 1 hour and 40 minutes. The reaction mixture was recooled to −78° C. and 2,2-dimethyl-4(2-methyl-thien-5-yl)-thiochrom-3-en-6-al (Compound U, 180 mg, 0.58 mmol) in THF (2 mL) was added. The reaction mixture was gradually warmed to −10° C. over 2 hours. Then the reaction was quenched by adding water (5 mL) and ethyl acetate (70 mL). The organic layer was washed with brine (10 mL) dried and the solvent was removed by distillation. The product E and Z isomers were isolated by column chromatography. The required E (minor) isomer (45 mg) was dissolved in dichloromethane (5 mL) and cooled to −78° C. To this solution SnCl4 (110 mg, 0.42 mmol) in dichloromethane (1 mL) was added dropwise, the reaction mixture was gradually warmed to −30° C. over 30 min. The reaction was quenched by adding ethanol (0.5 mL), water (5 mL) and ethyl acetate (75 mL). The organic layer was washed with brine (10 mL), dried and the solvent was removed by distillation. The title compound was isolated as a white solid after column chromatography.

Workup

  1. customwas recooled to −78° C.
  2. temperatureThe reaction mixture was gradually warmed to −10° C. over 2 hours
  3. customThen the reaction was quenched
  4. additionby adding water (5 mL) and ethyl acetate (70 mL)
  5. washThe organic layer was washed with brine (10 mL)
  6. customdried
  7. customthe solvent was removed by distillation

Sources & evidence

ORD record
ord-82305c0d00ab43c19eda102cfb7daa2d
Source dataset
uspto-grants-2007_01
Patent number
US07166726B2

Reaction notes

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