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

HRID 471219Notes

Reaction equation

HRID 471219 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Si]([O:32][CH2:33][CH2:34][C:35]1[C:36]([F:53])=[C:37]([CH:50]=[CH:51][CH:52]=1)[CH2:38][N:39]1[CH2:49][CH2:48][C:42]2([O:47][CH2:46][CH2:45][NH:44][CH2:43]2)[CH2:41][CH2:40]1)(C(C)(C)C)(C)C.[CH2:54]([C:56]1[S:60][CH:59]=[C:58]([C:61](O)=[O:62])[CH:57]=1)[CH3:55].C(N(CC)CC)C>CN(C=O)C>[CH2:54]([C:56]1[S:60][CH:59]=[C:58]([C:61]([N:44]2[CH2:43][C:42]3([CH2:41][CH2:40][N:39]([CH2:38][C:37]4[CH:50]=[CH:51][CH:52]=[C:35]([CH2:34][CH2:33][OH:32])[C:36]=4[F:53])[CH2:49][CH2:48]3)[O:47][CH2:46][CH2:45]2)=[O:62])[CH:57]=1)[CH3:55]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 35615485-Ethylthiophene-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579891399-(3-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-1-oxa-4,9-diazaspiro[5.5]undecane

Product 1

HCID 57989341(5-Ethylthiophen-3-yl)(9-(2-fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

HATU (0.316 g) was added in one portion to a solution at 0° C. of 9-(3-(2-(tert-butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-1-oxa-4,9-diazaspiro[5.5]undecane (example 78, step d) (0.271 g) and 5-ethylthiophene-3-carboxylic acid (0.1 g) and triethylamine (0.36 mL) in DMF (10 mL). The mixture was then stirred at 20° C. for 1 hour. The reaction mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The residue was dissolved in THF (20 mL) and treated with tetrabutylammonium fluoride (1M in THF, 1.921 mL). The reaction mixture was allowed to stand at 20° C. for 18 hours and the solvent was then removed under reduced pressure. The crude product was purified by flash silica chromatography using 2% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.12 g.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and brine
  2. washthe organic layer was washed twice with brine
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. customthe solvent evaporated under reduced pressure
  6. dissolutionThe residue was dissolved in THF (20 mL)
  7. additiontreated with tetrabutylammonium fluoride (1M in THF, 1.921 mL)
  8. waitto stand at 20° C. for 18 hours
  9. customthe solvent was then removed under reduced pressure
  10. customThe crude product was purified by flash silica chromatography
  11. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-969fbbe3c49f47e3b9c232582df6de41
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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