Trifluoroacetic acid → (5-Ethylthiophen-3-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

HRID 471225Notes

Reaction equation

HRID 471225 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[O:26]1[C:31]2([CH2:36][CH2:35][N:34](C(OC(C)(C)C)=O)[CH2:33][CH2:32]2)[CH2:30][NH:29][CH2:28][CH2:27]1.[CH2:44]([C:46]1[S:50][CH:49]=[C:48]([C:51](O)=[O:52])[CH:47]=1)[CH3:45].[F:54][C:55]([F:60])([F:59])[C:56]([OH:58])=[O:57]>CN(C=O)C.C1(C)C=CC=CC=1.C(Cl)Cl.C(N(CC)CC)C>[F:54][C:55]([F:60])([F:59])[C:56]([OH:58])=[O:57].[CH2:44]([C:46]1[S:50][CH:49]=[C:48]([C:51]([N:29]2[CH2:30][C:31]3([CH2:32][CH2:33][NH:34][CH2:35][CH2:36]3)[O:26][CH2:27][CH2:28]2)=[O:52])[CH:47]=1)[CH3:45]

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 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 66964240Tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride

Product 1

HCID 67292030(5-Ethylthiophen-3-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
20 °C

Procedure

HATU (1.15 g) was added in one portion to a solution at 0° C. of tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (WuXi PharmaTech) (0.682 g) and 5-ethylthiophene-3-carboxylic acid (0.364 g) and triethylamine (1.3 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 crude product was purified by flash silica chromatography using 50% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford the ‘BOC’ protected intermediate. DCM (10 mL) was added followed by trifluoroacetic acid (10 mL) and the resultant solution allowed to stand at 20° C. for 25 minutes. Toluene (30 mL) was added and the solvents evaporated under reduced pressure. The residue was azeotroped twice with acetonitrile to yield the subtitled compound. Yield 0.950 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. customThe crude product was purified by flash silica chromatography
  7. customPure fractions were evaporated to dryness
  8. customto afford the ‘BOC’
  9. waitto stand at 20° C. for 25 minutes
  10. customthe solvents evaporated under reduced pressure
  11. customThe residue was azeotroped twice with acetonitrile

Sources & evidence

ORD record
ord-4b2ecb0f3372472e8eacadee39f100e6
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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