Potassium Carbonate → (9-(3-(2-Hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 1255328Notes

Reaction equation

HRID 1255328 reaction equation
Cl.[CH:2]([C:5]1[S:6][CH:7]=[C:8]([C:10]([N:12]2[CH2:17][C:16]3([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[O:15][CH2:14][CH2:13]2)=[O:11])[N:9]=1)([CH3:4])[CH3:3].Br[CH2:24][CH2:25][C:26]1[CH:27]=[C:28]([CH2:32][CH2:33][OH:34])[CH:29]=[CH:30][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[OH:34][CH2:33][CH2:32][C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=1)[CH2:25][CH2:24][N:20]1[CH2:19][CH2:18][C:16]2([O:15][CH2:14][CH2:13][N:12]([C:10]([C:8]3[N:9]=[C:5]([CH:2]([CH3:4])[CH3:3])[S:6][CH:7]=3)=[O:11])[CH2:17]2)[CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 581685432-(3-(2-Bromoethyl)phenyl)ethanolHCID 66964119(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride

Product 1

HCID 58168488(9-(3-(2-Hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride [Example 27, step a] (10 g) and 2-(3-(2-bromoethyl)phenyl)ethanol [Organometallics 2002, 21(20), 4217] (10 g) and potassium carbonate (16 g) in acetonitrile (600 mL) and water (10 mL) was heated at 60° C. for 36 hours. The solvent was decanted off and evaporated under reduced pressure. The residue was partitioned between ethyl acetate and brine, the aqueous layer was re-extracted with ethyl acetate, and the combined organic layers were dried, filtered and the solvent evaporated under reduced pressure. The residue was purified by flash silica chromatography, using 5% methanol in ethyl acetate containing 1% triethylamine as solvent. Fractions containing the product were evaporated to dryness to afford the subtitled compound. Yield 11 g.

Workup

  1. customThe solvent was decanted off
  2. customevaporated under reduced pressure
  3. customThe residue was partitioned between ethyl acetate and brine
  4. extractionthe aqueous layer was re-extracted with ethyl acetate
  5. customthe combined organic layers were dried
  6. filtrationfiltered
  7. customthe solvent evaporated under reduced pressure
  8. customThe residue was purified by flash silica chromatography
  9. additionFractions containing the product
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-8e7b991e796e4179980af96a274c390a
Source dataset
uspto-grants-2013_06
Patent number
US08455483B2

Reaction notes

Loading…