Diethyl Ether → HCID 54525671, compound

HRID 963689Notes

Reaction equation

HRID 963689 reaction equation
[CH:1]1([NH:4][C:5]([CH:7]([NH:12][C:13]([CH:15]([C:20](=[CH2:24])[C:21]([OH:23])=[O:22])[CH2:16][CH:17]([CH3:19])[CH3:18])=[O:14])[C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])[CH2:3][CH2:2]1.[SH:25][C:26]1[S:27][CH:28]=[CH:29][CH:30]=1.C(OCC)C>CO>[CH:1]1([NH:4][C:5]([CH:7]([NH:12][C:13]([CH:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH:20]([CH2:24][S:25][C:26]2[S:27][CH:28]=[CH:29][CH:30]=2)[C:21]([OH:23])=[O:22])=[O:14])[C:8]([CH3:10])([CH3:9])[CH3:11])=[O:6])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 5226742-ThiophenethiolHCID 54444274HCID 54444274, compound

Product 1

HCID 54525671HCID 54525671, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

2-[1-(1 -Cyclopropylcarbamoyl-2,2-dimethyl-propylcarbamoyl)-3-methyl-butyl]-acrylic acid (4.40 g, 12.4 mmol) was dissolved in methanol (10 ml) and placed under a blanket of argon prior to addition of 2-mercaptothiophene (4.5 ml). The mixture was stirred overnight at 60° C. under argon with the exclusion of light. The solvent was removed under reduced pressure to leave an oil to which was added cold diethyl ether (200 ml). The product precipitated on standing in an ice bath and was removed by filtration and washing with thoroughly with cold diethyl ether. The product was further purified by trituration with hot ethyl acetate and column chromatography (silica gel, gradient elution, 0-20% methanol in dichloromethane). Fractions were combined and evaporated to yield the title compound as an pale yellow solid (6.95 g, including minor impurities). 1H-NMR (CDCl3, partial deuterium exchange); δ 8.10 (1H, m), 7.85 (1H, d, J=9.2 Hz), 7.35 (1H, m), 7.03 (1H, m), 6.88 (1H, m), 4.06 (1H, d, J=9.2 Hz), 2.85 (1H, m), 2.67 (2H, m), 2.51 (1H, m), 1.53 (1H, m), 1.25 (1H, m), 1.02 (1H, m), 0.87 (9H, s), 0.76 (3H, d, J=6.4 Hz), 0.71 (3 H, d,J=6.5 Hz), 0.61 (2H, m) and 0.32 (2H, m).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto leave an oil to which
  3. customThe product precipitated
  4. customon standing in an ice bath
  5. customwas removed by filtration
  6. washwashing with thoroughly with cold diethyl ether
  7. customThe product was further purified by trituration with hot ethyl acetate and column chromatography (silica gel, gradient elution, 0-20% methanol in dichloromethane)
  8. customevaporated

Sources & evidence

ORD record
ord-f08ceb946e8f4bb28b6a6d0b3a329626
Source dataset
uspto-grants-1998_06
Patent number
US05763621

Reaction notes

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