Methanol → 2-[2-(7-Ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]ethanol

HRID 1189044Notes

Reaction equation

HRID 1189044 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([O:24][C:25]2[CH:26]=[N:27][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][CH:30]=2)[CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]1[S:14][CH:15]([CH2:18][C:19](OCC)=[O:20])[CH2:16][N:17]=1)=[CH:9]2)[CH3:2].CO.[BH4-].[Li+]>O1CCCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([O:24][C:25]2[CH:26]=[N:27][C:28]([S:31]([CH3:34])(=[O:32])=[O:33])=[CH:29][CH:30]=2)[CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]1[S:14][CH:15]([CH2:18][CH2:19][OH:20])[CH2:16][N:17]=1)=[CH:9]2)[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 4148881Lithium borohydride2×HCID 58237074Ethyl [2-(7-ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetate

Product 1

HCID 582371202-[2-(7-Ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]ethanolYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cooled and stirred solution of ethyl [2-(7-ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetate (110 mg) in tetrahydrofuran (8 mL)-methanol (2 mL) was added lithium borohydride (25 mg), and the mixture was stirred at room temperature for 4 h, followed by an addition of lithium borohydride (25 mg). After stirring at room temperature for 3 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=50:50 to 100:0, volume ratio) to give a colorless oil, which was crystallized from ethyl acetate-hexane to give the title compound (54 mg, 54%) as colorless crystals. MS 462 (MH+). mp 147-148° C.

Workup

  1. stirringAfter stirring at room temperature for 3 h
  2. customthe reaction mixture was partitioned between ethyl acetate and aqueous citric acid solution
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (ethyl acetate:hexane=50:50 to 100:0, volume ratio)
  8. customto give a colorless oil, which
  9. customwas crystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-b158acef402840558c49bfc9bb9f9e9a
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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