Methanol → 2-((S)-6-((R)-7-Fluoro-4-(4-(2-methoxy-2-oxoethoxy)-2,6-dimethylphenyl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetic acid

HRID 237462Notes

Reaction equation

HRID 237462 reaction equation
[OH-:1].[Na+].[C:3]([CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([C:14]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]3[C:15]=2[CH2:16][CH2:17][C@H:18]3[O:24][C:25]2[CH:38]=[CH:37][C:28]3[C@H:29]([CH2:32][C:33]([O:35]C)=[O:34])[CH2:30][O:31][C:27]=3[CH:26]=2)=[C:9]([CH3:39])[CH:8]=1)#N.[CH3:40][OH:41]>>[F:23][C:20]1[CH:21]=[CH:22][C:14]([C:10]2[C:9]([CH3:39])=[CH:8][C:7]([O:6][CH2:5][C:3]([O:41][CH3:40])=[O:1])=[CH:12][C:11]=2[CH3:13])=[C:15]2[C:19]=1[C@H:18]([O:24][C:25]1[CH:38]=[CH:37][C:28]3[C@H:29]([CH2:32][C:33]([OH:35])=[O:34])[CH2:30][O:31][C:27]=3[CH:26]=1)[CH2:17][CH2:16]2

Participants

4

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 86697125Methyl 2-((S)-6-((R)-4-(4-(cyanomethoxy)-2,6-dimethylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

Product 1

HCID 866971262-((S)-6-((R)-7-Fluoro-4-(4-(2-methoxy-2-oxoethoxy)-2,6-dimethylphenyl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetic acid

Procedure

A 1 M aqueous NaOH solution (400 μL) is added to a solution of methyl 2-((S)-6-((R)-4-(4-(cyanomethoxy)-2,6-dimethylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate (120 mg) in methanol (4 mL). The mixture is stirred for 12 hours at room temperature. Methanol is evaporated off in vacuo and the residue is diluted with water. 1 M hydrochloric acid (400 μL) is added and the aqueous phase is extracted twice with dichloromethane The combined organic phases are dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (petrole ether/ethyl acetate 60:40→0:100). The product thus obtained is crystallized from n-hexane to give the title compound. Yield: 75 mg; LC (method 7): tR=0.99 min; Mass spectrum (ESI+): m/z=521 [M+H]+.

Workup

  1. customMethanol is evaporated off in vacuo
  2. additionthe residue is diluted with water
  3. addition1 M hydrochloric acid (400 μL) is added
  4. extractionthe aqueous phase is extracted twice with dichloromethane The combined organic phases
  5. dry with materialare dried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel (petrole ether/ethyl acetate 60:40→0:100)
  8. customThe product thus obtained
  9. customis crystallized from n-hexane

Sources & evidence

ORD record
ord-9fe14f0aa98744bdb4e7f4ded9efb671
Source dataset
uspto-grants-2014_02
Patent number
US08642585B2

Reaction notes

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