Sodium Hydroxide → 3-{4-[3-(3-Ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-3-oxo-propenyl]-2,6-dimethyl-phenyl}-propionic acid

HRID 1013442Notes

Reaction equation

HRID 1013442 reaction equation
[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:10])[CH3:9])=[C:5]2[CH2:11][CH2:12][C:13]([CH3:16])([CH3:15])[CH2:14][C:4]=12)[CH3:2].[CH:17]([C:19]1[CH:24]=[C:23]([CH3:25])[C:22]([CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[C:21]([CH3:31])[CH:20]=1)=O.[OH-].[Na+]>CO.Cl>[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:10])[CH:9]=[CH:17][C:19]2[CH:24]=[C:23]([CH3:25])[C:22]([CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[C:21]([CH3:31])[CH:20]=2)=[C:5]2[CH2:11][CH2:12][C:13]([CH3:15])([CH3:16])[CH2:14][C:4]=12)[CH3:2]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 574374043-(4-Formyl-2,6-dimethyl-phenyl)-propionic acidHCID 574374251-(3-Ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-ethanone

Product 1

HCID 673169693-{4-[3-(3-Ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-3-oxo-propenyl]-2,6-dimethyl-phenyl}-propionic acidYield 86.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

A solution of 1-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-ethanone (400 mg, 1.69 mmol), 3-(4-formyl-2,6-dimethyl-phenyl)-propionic acid (419 mg, 2.03 mmol) and NaOH (1.7 g, 42.5 mmol) in methanol (17 mL) is stirred at 75° C. for 75 min before it is diluted with 1 N aq. HCl and extracted twice with EA. The organic extracts are dried over MgSO4, filtered and evaporated. The crude product is purified by CC on silica gel eluting with DCM containing 6% of methanol to give 3-{4-[3-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-3-oxo-propenyl]-2,6-dimethyl-phenyl}-propionic acid (620 mg) as a pale yellow solid; LC-MS: tR=1.17 min; [M+1]=425.34; 1H NMR (CDCl3): δ 7.68 (d, J=15.8 Hz, 1H), 7.28 (s, 2H), 7.27 (d, J=15.8 Hz, 1H), 3.18 (t, J=7.0 Hz, 2H), 3.06-2.98 (m, 2H), 2.78 (q, J=7.6 Hz, 2H), 2.54-2.48 (m, 2H), 2.39 (s, 6H), 2.34 (s, 2H), 1.58 (t, J=7.0 Hz, 2H), 1.32 (t, J=7.6 Hz, 3H).

Workup

  1. extractionextracted twice with EA
  2. dry with materialThe organic extracts are dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product is purified by CC on silica gel eluting with DCM containing 6% of methanol

Sources & evidence

ORD record
ord-657c28ef7a6a429aa7918709a88b4841
Source dataset
uspto-grants-2011_07
Patent number
US07981924B2

Reaction notes

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