Triethylamine → (5-Ethylthiophen-3-yl)(9-(4-fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

HRID 471226Notes

Reaction equation

HRID 471226 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.[CH2:20]([C:22]1[S:26][CH:25]=[C:24]([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])[CH:23]=1)[CH3:21].C(N(CC)CC)C>C(#N)C>[CH2:20]([C:22]1[S:26][CH:25]=[C:24]([C:27]([N:29]2[CH2:34][C:33]3([CH2:39][CH2:38][N:37]([CH2:2][C:3]4[CH:4]=[CH:5][C:6]([F:12])=[C:7]([CH2:9][CH2:10][OH:11])[CH:8]=4)[CH2:36][CH2:35]3)[O:32][CH2:31][CH2:30]2)=[O:28])[CH:23]=1)[CH3:21]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 579890232-(5-(Bromomethyl)-2-fluorophenyl)ethanolHCID 67292030(5-Ethylthiophen-3-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57989276(5-Ethylthiophen-3-yl)(9-(4-fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

2-(5-(Bromomethyl)-2-fluorophenyl)ethanol (example 47, step a) (0.171 g) was added to a solution of (5-ethylthiophen-3-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 99, step a) (0.3 g) and triethylamine (0.410 ml) in acetonitrile (15 mL) and the mixture stirred at 20° C. for 2 hours. The solvent was evaporated under reduced pressure and the residue partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 1% triethylamine and 2% methanol in dichloromethane as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.2 g.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue partitioned between ethyl acetate and saturated sodium bicarbonate solution
  3. dry with materialThe organic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. customthe solvent evaporated under reduced pressure
  6. customThe crude product was purified by flash silica chromatography
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-643e1f4404d54b099362ad7e11c9c13b
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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