Triethylamine → Tert-butyl 2,2-difluoro-4-(5-methylthiophene-2-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 1689282Notes

Reaction equation

HRID 1689282 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1([F:44])[CH2:31][NH:30][CH2:29][C:28]2([CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]2)[O:27]1.[CH3:45][C:46]1[S:50][C:49]([C:51](O)=[O:52])=[CH:48][CH:47]=1.C(N(CC)CC)C>CN(C=O)C>[F:44][C:26]1([F:25])[CH2:31][N:30]([C:51]([C:49]2[S:50][C:46]([CH3:45])=[CH:47][CH:48]=2)=[O:52])[CH2:29][C:28]2([CH2:32][CH2:33][N:34]([C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])[CH2:35][CH2:36]2)[O:27]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 747135-Methylthiophene-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57989014tert-Butyl 2,2-difluoro-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 57989071Tert-butyl 2,2-difluoro-4-(5-methylthiophene-2-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

HATU (0.541 g) was added in one portion to a stirred solution at 0° C. of tert-butyl 2,2-difluoro-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (example 37, step c) (0.32 g) and 5-methylthiophene-2-carboxylic acid (0.171 g) and triethylamine (0.458 mL) in DMF (20 mL). The mixture was then stirred at 20° C. for 7 hours. The 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, elution gradient 0.5 to 5% methanol in dichloromethane. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.4 g.

Workup

  1. customThe 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, elution gradient 0.5 to 5% methanol in dichloromethane
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-dd6f16d43c8648caaa07403c4184e16b
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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