Iodoethane → Ethoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid

HRID 2406384Notes

Reaction equation

HRID 2406384 reaction equation
C([O:3][C:4](=[O:32])[CH:5]([C:7]1[C:8]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=2[O:28]CC=C)=[C:9]2[C:16]3[CH2:17][CH2:18][CH2:19][CH2:20][C:15]=3[S:14][C:10]2=[N:11][C:12]=1[CH3:13])[OH:6])C.I[CH2:34][CH3:35]>CC#N.[Ag]=O.[Ag-]=O>[CH2:34]([O:6][CH:5]([C:7]1[C:8]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=2[OH:28])=[C:9]2[C:16]3[CH2:17][CH2:18][CH2:19][CH2:20][C:15]=3[S:14][C:10]2=[N:11][C:12]=1[CH3:13])[C:4]([OH:3])=[O:32])[CH3:35]

Participants

6

Reactant 2

HCID 6340Iodoethane2×HCID 69672380Ethyl {4-[2-(allyloxy)-4-methylphenyl]-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl}(hydroxy)acetate

Product 1

HCID 136372353Ethoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acidYield 22%

Reagents, catalysts & solvents 3

HCID 92152Silver(II) oxideCatalystHCID 178418778HCID 178418778, compoundCatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

To a stirred solution of [4-(2-Allyloxy-4-methyl-phenyl)-2-methyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-b]pyridin-3-yl]-hydroxy-acetic acid ethyl ester (100 mg, 221 μmols, 1 eq) in MeCN (5 mL) was added silver oxide (102 mg, 442 μmols, 2 eq) followed by iodoethane (172 mg, 89 uL, 5 eq) and the reaction was stirred for 16 hours at 60° C. Additional iodoethane (1 mL, 50 eq) and silver (I) oxide (102 mg, 2 eq) was added and the reaction was continued to be heated at 60° C. for 16 hours. The reaction was diluted with MeCN (5 mL), and filtered. The filtrate was then concentrated in vacuo. The residue was purified using ISCO Companion with a Redisep silica gel 12 g cartridge and a gradient of heptane and ethyl acetate (0% to 30%). Fractions containing [4-(2-allyloxy-4-methyl-phenyl)-2-methyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-b]pyridin-3-yl]-ethoxy-acetic acid ethyl ester were combined and concentrated in vacuo to give the desired product as a pale orange oil, 22 mg (22% yield). LC-MS (12 min acidic) 7.55 mins 100% pure by UV, ES+/APCI+ 480.

Workup

  1. temperatureto be heated at 60° C. for 16 hours
  2. filtrationfiltered
  3. concentrationThe filtrate was then concentrated in vacuo
  4. customThe residue was purified
  5. additionFractions containing [4-(2-allyloxy-4-methyl-phenyl)-2-methyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-b]pyridin-3-yl]-ethoxy-acetic acid ethyl ester
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3f2913c088554901b028b495118b069d
Source dataset
uspto-grants-2014_08
Patent number
US08809363B2

Reaction notes

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