Tetrahydrofuran → Enrasentan

HRID 277499Notes

Reaction equation

HRID 277499 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]3[C:18]4[C:13](=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH3:22])=[CH:16][CH:17]=4)[CH:12]([C:23]4[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][C:24]=4[O:31][CH2:32][CH2:33][OH:34])[CH:11]3[C:35]([O:37]C)=[O:36])=[CH:9][C:4]=2[O:3][CH2:2]1.C1COCC1.O[Li].O.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O.CCOC(C)=O.CO>[OH:34][CH2:33][CH2:32][O:31][C:24]1[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:23]=1[C@@H:12]1[C:13]2[C:18](=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH2:21][CH3:22])[CH:14]=2)[C@H:10]([C:8]2[CH:7]=[CH:6][C:5]3[O:1][CH2:2][O:3][C:4]=3[CH:9]=2)[C@H:11]1[C:35]([OH:37])=[O:36]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 168937Lithium hydroxide, monohydrateHCID 22117957HCID 22117957, compound

Product 1

HCID 178103EnrasentanYield 83.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 10 mL three-necked flask equipped with reflux condenser was charged with [1S -(1α, 2α, 3α)]-methyl 1-(1,3-benzodioxol-5-yl)-2,3-dihydro-3-[2-(2-hydroxyethoxy)-4-methoxyphenyl]-5-propoxy-1H-indene-2-carboxylate (34 mg, 0.071 mmol), THF (1 mL), MeOH (0.5 mL) and LiOH—H2O (15 mg, 0.355 mmol). The solution was heated to reflux for 12 h, cooled to room temperature and acidified with citric acid monohydrate (40 mg, 0.19 mmol) to pH 3.0. Upon complete hydrolysis, EtOAc (20 mL) and H2O (20 mL) was added, the organic phase washed with brine (15 mL), dried (MgSO4) and concentrated in vacuo affording (+) (1S, 2R, 3S)-3-[2-(2-hydroxyeth-1-yloxy)-4methoxyphenyl]-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid as a white solid (30 mg, 81%).

Workup

  1. customA 10 mL three-necked flask equipped
  2. temperaturewith reflux condenser
  3. temperatureThe solution was heated
  4. temperatureto reflux for 12 h
  5. additionwas added
  6. washthe organic phase washed with brine (15 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-377e14bac513469f946d9d0aaf624294
Source dataset
uspto-grants-2002_03
Patent number
US06355813B1

Reaction notes

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