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

HRID 1689313Notes

Reaction equation

HRID 1689313 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([F:12])=[C:7]([CH2:9][CH2:10][OH:11])[CH:8]=1.FC(F)(F)C(O)=O.[CH:20]([C:23]1[S:24][CH:25]=[C:26]([C:28]([N:30]2[CH2:35][C:34]3([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[O:33][CH2:32][CH2:31]2)=[O:29])[N:27]=1)([CH3:22])[CH3:21].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[F:12][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][N:38]2[CH2:39][CH2:40][C:34]3([O:33][CH2:32][CH2:31][N:30]([C:28]([C:26]4[N:27]=[C:23]([CH:20]([CH3:21])[CH3:22])[S:24][CH:25]=4)=[O:29])[CH2:35]3)[CH2:36][CH2:37]2)=[CH:8][C:7]=1[CH2:9][CH2:10][OH:11]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 579890232-(5-(Bromomethyl)-2-fluorophenyl)ethanolHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57989065(9-(4-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-(5-(Bromomethyl)-2-fluorophenyl)ethanol (example 47A, step a) (5.2 g) was added to a suspension of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (9.4 g) and potassium carbonate (6.8 g) in ethanol (75 mL). The resulting mixture was stirred overnight and filtered. The filter cake was washed with ethanol (50 mL) and the combined filtrate and washings were evaporated. The residue was partioned between water (100 mL) and ethyl acetate (250 mL), The layers were separated and the organic washed with brine (100 mL), dried over sodium sulphate, filtered and evaporated. Purification was by silica gel chromatography eluting with 95:5 ethyl acetate:triethylamine gradient. The fractions containing product were combined and evaporated to give to the subtitled compound as a yellow gum. Yield 7.9 g.

Workup

  1. filtrationfiltered
  2. washThe filter cake was washed with ethanol (50 mL)
  3. customthe combined filtrate and washings were evaporated
  4. customThe layers were separated
  5. washthe organic washed with brine (100 mL)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customPurification
  10. washeluting with 95:5 ethyl acetate
  11. additionThe fractions containing product
  12. customevaporated

Sources & evidence

ORD record
ord-c677909e9a274afb93e11f373d6bb6cc
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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