Potassium Hydroxide → (-)-7-{[5-(1-Cyclopropyl-2,2,2-trifluoro-1-hydroxyethyl)-1,3-thiazol-2-yl]thio}-4-pyridin-3-yl-2H-chromen-2-one

HRID 2116652Notes

Reaction equation

HRID 2116652 reaction equation
[OH-].[K+].[CH:3]1([C:6]([C:12]2[S:16][C:15]([SH:17])=[N:14][CH:13]=2)([OH:11])[C:7]([F:10])([F:9])[F:8])[CH2:5][CH2:4]1.Br[C:19]1[CH:28]=[C:27]2[C:22]([C:23]([C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)=[CH:24][C:25](=[O:29])[O:26]2)=[CH:21][CH:20]=1>CO>[CH:3]1([C:6]([C:12]2[S:16][C:15]([S:17][C:19]3[CH:28]=[C:27]4[C:22]([C:23]([C:30]5[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=5)=[CH:24][C:25](=[O:29])[O:26]4)=[CH:21][CH:20]=3)=[N:14][CH:13]=2)([OH:11])[C:7]([F:8])([F:10])[F:9])[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 233702367-Bromo-4-(pyridin-3-yl)-2H-1-benzopyran-2-oneHCID 178519846HCID 178519846, compound

Product 1

HCID 11352007(-)-7-{[5-(1-Cyclopropyl-2,2,2-trifluoro-1-hydroxyethyl)-1,3-thiazol-2-yl]thio}-4-pyridin-3-yl-2H-chromen-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

Powdered KOH (0.111 g, 1.98 mmol) was added to a solution of (−)-1-cyclopropyl-2,2,2-trifluoro-1-(2-mercapto-1,3-thiazol-5-yl)ethanol (0.507 g, 1.98 mmol) in dry MeOH (2 mL). When a solution was obtained, the reaction mixture was concentrated to dryness. Dry toluene was then added and the mixture was concentrated to dryness again. The residue was dissolved in NMP (2 mL) and 7-bromo-4-pyridin-3-yl-2H-chromen-2-one (0.500 g, 1.65 mmol) was added and the resulting mixture was stirred at 120° C. for 16 h. Once cooled, the mixture was directly applied onto a column of silica gel and chromatographed (acetone/toluene 5:95 to 20:80), affording the title compound. 1H NMR (500 MHz, CDCl3): δ 8.76 (brd, 1H), 8.68 (d, 1H), 7.85 (s, 1H), 7.79 (brd, 1H), 7.50 (m, 2H), 7.31-7.36 (m, 2H), 6.39 (s, 1H), 3.05 (br s, 1H), 1.48 (m, 1H), 0.71 (m, 2H), 0.62 (m, 1H), 0.56 (m, 1H); [α]D=−31.1° (c=1.05, EtOH).

Workup

  1. customWhen a solution was obtained
  2. concentrationthe reaction mixture was concentrated to dryness
  3. additionDry toluene was then added
  4. concentrationthe mixture was concentrated to dryness again
  5. dissolutionThe residue was dissolved in NMP (2 mL)
  6. temperatureOnce cooled
  7. customchromatographed (acetone/toluene 5:95 to 20:80)

Sources & evidence

ORD record
ord-97014e6d1ab648928219696b0a34db2f
Source dataset
uspto-grants-2008_10
Patent number
US07439260B2

Reaction notes

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