Cesium carbonate → (2-Ethylthiazol-4-yl)(9-(4-(2-hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

HRID 1255304Notes

Reaction equation

HRID 1255304 reaction equation
Br[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][OH:12])=[CH:6][CH:5]=1.FC(F)(F)C(O)=O.[CH2:20]([C:22]1[S:23][CH:24]=[C:25]([C:27]([N:29]2[CH2:34][C:33]3([CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)[O:32][CH2:31][CH2:30]2)=[O:28])[N:26]=1)[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.O>[CH2:20]([C:22]1[S:23][CH:24]=[C:25]([C:27]([N:29]2[CH2:34][C:33]3([CH2:39][CH2:38][N:37]([CH2:2][CH2:3][C:4]4[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][OH:12])=[CH:6][CH:5]=4)[CH2:36][CH2:35]3)[O:32][CH2:31][CH2:30]2)=[O:28])[N:26]=1)[CH3:21]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 669633682-(4-(2-Bromoethyl)phenyl)ethanol2×HCID 66964094(2-Ethylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 58168519(2-Ethylthiazol-4-yl)(9-(4-(2-hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
75 °C

Procedure

A solution of 2-(4-(2-bromoethyl)phenyl)ethanol [Organometallics 2002, 21(20), 4217] (1.71 g) in NMP (5 mL) was added to a suspension of (2-ethylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate [Example 3, step b] (3.0 g) and cesium carbonate (5.60 g) in NMP (10 mL) and the mixture stirred at 75° C. under nitrogen for 4 hours. More 2-(4-(2-bromoethyl)phenyl)ethanol (0.65 g) was added and the mixture stirred at 75° C. for 18 hours. The mixture was cooled, diluted with water and extracted into ethyl acetate (×3). The combined extracts were washed with 10% brine, 30% brine and saturated brine, dried over magnesium sulfate, filtered and the solvent removed. The crude product was purified by flash silica chromatography, successively eluted with 50% ethyl acetate in isohexane with 5% triethylamine, then 100% ethyl acetate with 5% triethylamine, then 10% methanol in ethyl acetate with 5% triethylamine. Fractions containing the product were evaporated to dryness to afford the subtitled compound as a yellow oil. Yield 1.90 g.

Workup

  1. stirringthe mixture stirred at 75° C. for 18 hours
  2. temperatureThe mixture was cooled
  3. extractionextracted into ethyl acetate (×3)
  4. washThe combined extracts were washed with 10% brine, 30% brine and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent removed
  8. customThe crude product was purified by flash silica chromatography
  9. washsuccessively eluted with 50% ethyl acetate in isohexane with 5% triethylamine
  10. additionFractions containing the product
  11. customwere evaporated to dryness

Sources & evidence

ORD record
ord-9ba7f1d6d01d4541a0fd701d22af7d09
Source dataset
uspto-grants-2013_06
Patent number
US08455483B2

Reaction notes

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