Hydrochloric Acid → Methyl 5-[[[5-methoxy-3-(1-methylethoxy)benzo[b]thien2-yl]carbonyl]amino]pentanoate

HRID 247910Notes

Reaction equation

HRID 247910 reaction equation
[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]2[S:7][C:8]([C:14]([OH:16])=O)=[C:9]([O:10][CH:11]([CH3:13])[CH3:12])[C:5]=2[CH:4]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]([O:39][CH3:40])=[O:38].C(N(CC)CC)C>O1CCCC1>[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]2[S:7][C:8]([C:14]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]([O:39][CH3:40])=[O:38])=[O:16])=[C:9]([O:10][CH:11]([CH3:12])[CH3:13])[C:5]=2[CH:4]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 10964545Methyl 5-aminopentanoateHCID 139616485-Methoxy-3-(1-methylethoxy)benzo[b]thiophene-2-carboxylic acid

Product 1

HCID 10643446Methyl 5-[[[5-methoxy-3-(1-methylethoxy)benzo[b]thien2-yl]carbonyl]amino]pentanoateYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-methoxy-3-(1-methylethoxy)benzo[b]thiophene-2-carboxylic acid (500 mg, 2.00 mmoles) and 1,1'-carbonyldiimidazole (421 mg, 2.60 mmoles) in 20 mL of tetrahydrofuran is heated at reflux for 1 hour. After cooling to 0° C., the HCl salt of methyl 5-aminovalerate (787 mg, 4.7 mmoles) is added followed by triethylamine (836 μL, 6.0 mmoles). The mixture is heated at reflux overnight. The mixture is partitioned between ethyl acetate and 1N HCl. The organic layer is washed with 1N HCl, saturated NaHCO3, then brine. The organic layer is next dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product is purified by flash chromatography, eluting with 1:9 ethyl acetate:hexane to provide 530 mg (70%) of product; mp 82°-84° C.

Workup

  1. temperatureat reflux for 1 hour
  2. temperatureThe mixture is heated
  3. temperatureat reflux overnight
  4. customThe mixture is partitioned between ethyl acetate and 1N HCl
  5. washThe organic layer is washed with 1N HCl, saturated NaHCO3
  6. dry with materialThe organic layer is next dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product is purified by flash chromatography
  10. washeluting with 1:9 ethyl acetate

Sources & evidence

ORD record
ord-cb27f95425b749a19e65be8b0b48e30e
Source dataset
uspto-grants-1993_05
Patent number
US05208253

Reaction notes

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