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

HRID 471053Notes

Reaction equation

HRID 471053 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][OH:11])[CH:6]=[CH:7][CH:8]=1.FC(F)(F)C(O)=O.[F:19][C:20]1([F:39])[CH2:25][N:24]([C:26]([C:28]2[S:29][C:30]([CH3:33])=[CH:31][CH:32]=2)=[O:27])[CH2:23][C:22]2([CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[O:21]1.C(N(CC)CC)C>C(#N)C>[F:39][C:20]1([F:19])[CH2:25][N:24]([C:26]([C:28]2[S:29][C:30]([CH3:33])=[CH:31][CH:32]=2)=[O:27])[CH2:23][C:22]2([CH2:34][CH2:35][N:36]([CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH2:10][OH:11])[CH:4]=3)[CH2:37][CH2:38]2)[O:21]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 18999576Benzeneethanol, 3-(bromomethyl)-HCID 67291912(2,2-Difluoro-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-methylthiophen-2-yl)methanone trifluoroacetate

Product 1

HCID 57989272(2,2-Difluoro-9-(3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-methylthiophen-2-yl)methanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

2-(3-(Bromomethyl)phenyl)ethanol (example 6, step a) (0.095 g) was added to a solution of (2,2-difluoro-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-methylthiophen-2-yl)methanone trifluoroacetate (example 37, step e) (0.19 g) and triethylamine (0.185 mL) in acetonitrile (10 mL) and the reaction mixture stirred at 20° C. for 3 hours. The solvent was evaporated under reduced pressure and the residue partitioned between ethyl acetate and brine, 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 2.5% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.188 g.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue partitioned between ethyl acetate and brine
  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-ab5a1d5604df47e987b74818f2ff778d
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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