Sodium Methoxide → HCID 57508896, compound

HRID 1665945Notes

Reaction equation

HRID 1665945 reaction equation
C(O[C:4]([C:6]1[S:7][C:8](Br)=[C:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][C:10]=12)=[O:5])C.[CH3:18][O-:19].[Na+].[CH3:21][Li]>CO.CCOCC>[CH3:18][O:19][C:8]1[S:7][C:6]([C:4](=[O:5])[CH3:21])=[C:10]2[CH2:11][CH2:12][C:13]([CH3:15])([CH3:16])[CH2:14][C:9]=12

Participants

6

Reactant 3

HCID 10942334Sodium MethoxideHCID 57437427HCID 57437427, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 57508896HCID 57508896, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent3×

Procedure

A mixture of crude 3-bromo-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid ethyl ester (774 mg, 2.44 mmol), CuO (99 mg, 1.25 mmol) and NaOMe (540 mg, 10 mmol) in methanol (3 mL) is refluxed for 76 h. The mixture is diluted with ether (75 mL) and extracted with 1 N aq. NaOH (2×30 mL). The aq. extracts are acidified with 2 N aq. HCl (75 mL) and extracted with DCM (3×50 mL). The organic extracts are dried (Na2SO4), filtered and evaporated to provide crude 3-methoxy-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (262 mg). This material is dissolved in dry diethyl ether (10 mL) and methyllithium (0.7 mL, 1.6 N in diethyl ether) is added slowly at room temperature. After 15 min, the mixture is diluted with diethyl ether (50 mL), extracted with 1 N aq. NaOH (2×5 mL), dried (Na2SO4), filtered and evaporated. The crude product is purified by CC on silica gel eluting with heptane/EA to provide 1-(3-methoxy-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-ethanone (44 mg) as a yellow oil; LC-MS: tR=1.03 min, [M+1]=239.30; 1H NMR (CDCl3): δ 3.96 (s, 3H), 2.98 (t, J=6.4 Hz, 2H), 2.41 (s, 3H), 2.26 (s, 2H), 1.53 (t, J=6.4 Hz, 2H), 0.95 (s, 6H).

Workup

  1. temperatureis refluxed for 76 h
  2. extractionextracted with 1 N aq. NaOH (2×30 mL)
  3. extractionextracted with DCM (3×50 mL)
  4. dry with materialThe organic extracts are dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto provide crude 3-methoxy-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (262 mg)
  8. extractionextracted with 1 N aq. NaOH (2×5 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated
  12. customThe crude product is purified by CC on silica gel eluting with heptane/EA

Sources & evidence

ORD record
ord-5713afb241a34a78ad70311f8bcc00d0
Source dataset
uspto-grants-2011_10
Patent number
US08039644B2

Reaction notes

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