Methanol → HCID 67118480, compound

HRID 1189039Notes

Reaction equation

HRID 1189039 reaction equation
[F:1][C:2]1[C:10]([O:11][CH2:12][CH2:13][O:14][CH3:15])=[C:9]2[C:5]([CH:6]=[C:7]([C:16]3[S:17][CH:18]([CH2:21][C:22](OCC)=[O:23])[CH2:19][N:20]=3)[NH:8]2)=[CH:4][C:3]=1[O:27][C:28]1[CH:29]=[N:30][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:32][CH:33]=1.CO.[BH4-].[Li+]>O1CCCC1>[F:1][C:2]1[C:10]([O:11][CH2:12][CH2:13][O:14][CH3:15])=[C:9]2[C:5]([CH:6]=[C:7]([C:16]3[S:17][CH:18]([CH2:21][CH2:22][OH:23])[CH2:19][N:20]=3)[NH:8]2)=[CH:4][C:3]=1[O:27][C:28]1[CH:29]=[N:30][C:31]([S:34]([CH3:37])(=[O:35])=[O:36])=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 4148881Lithium borohydride3×HCID 70963860HCID 70963860, compound

Product 1

HCID 67118480HCID 67118480, compoundYield 41.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cooled and stirred solution of ethyl {2-[6-fluoro-7-(2-methoxyethoxy)-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetate (200 mg) in tetrahydrofuran (8 mL)-methanol (6 mL) was added lithium borohydride (40 mg), and the mixture was stirred at room temperature for 2.5 h, followed by an addition of lithium borohydride (40 mg). After the mixture was stirred at room temperature for 2 h, lithium borohydride (40 mg) was further added thereto. After stirring at room temperature for 2 h, the reaction mixture was partitioned between ethyl acetate and aqueous citric acid solution. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated. The residue was purified by silica gel chromatography (ethyl acetate:hexane=60:40 to 100:0, volume ratio) to give colorless crystals, which were recrystallized from tetrahydrofuran-ethyl acetate-hexane to give the title compound (76 mg, 41%) as colorless crystals. MS 510 (MH+). mp 160-161° C.

Workup

  1. stirringAfter the mixture was stirred at room temperature for 2 h
  2. stirringAfter stirring at room temperature for 2 h
  3. customthe reaction mixture was partitioned between ethyl acetate and aqueous citric acid solution
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (ethyl acetate:hexane=60:40 to 100:0, volume ratio)
  9. customto give colorless crystals, which
  10. customwere recrystallized from tetrahydrofuran-ethyl acetate-hexane

Sources & evidence

ORD record
ord-5d7dac41cecf4f958c8974b302d7af81
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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