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

HRID 471190Notes

Reaction equation

HRID 471190 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[O:25]1[C:30]2([CH2:35][CH2:34][N:33]([CH2:36][C:37]3[CH:38]=[C:39]([CH2:43][CH2:44][OH:45])[CH:40]=[CH:41][CH:42]=3)[CH2:32][CH2:31]2)[CH2:29][NH:28][CH2:27][CH2:26]1.[CH:46]([C:49]1[S:53][CH:52]=[C:51]([C:54](O)=[O:55])[CH:50]=1)([CH3:48])[CH3:47].C(N(CC)CC)C>CN(C=O)C>[OH:45][CH2:44][CH2:43][C:39]1[CH:38]=[C:37]([CH:42]=[CH:41][CH:40]=1)[CH2:36][N:33]1[CH2:32][CH2:31][C:30]2([O:25][CH2:26][CH2:27][N:28]([C:54]([C:51]3[CH:50]=[C:49]([CH:46]([CH3:48])[CH3:47])[S:53][CH:52]=3)=[O:55])[CH2:29]2)[CH2:35][CH2:34]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 35250805-Isopropylthiophene-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 579893852-(3-(1-Oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)phenyl)ethanol

Product 1

HCID 57989123(9-(3-(2-Hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-isopropylthiophen-3-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.55 g) was added to a solution of 2-(3-(1-oxa-4,9-diazaspiro[5.5]undecan-9-ylmethyl)phenyl)ethanol (example 82, step a) (0.32 g), 5-isopropylthiophene-3-carboxylic acid (0.19 g) and triethylamine (0.61 mL) in DMF (7 mL) at 0° C. The resulting yellow solution was allowed to warm to RT and was stirred for 2 h. The mixture was partitioned between ethyl acetate (100 mL) and brine (100 mL), the organic phase was washed with brine (2×100 mL), dried over sodium sulphate, filtered and the solvent evaporated. The resulting gum was purified by silica gel chromatography eluting with 47.5:47.5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient. The fractions containing product were combined, toluene (200 mL) was added, and the solvent evaporated under reduced pressure to give the subtitled compound as a clear gum. Yield 0.4 g.

Workup

  1. customThe mixture was partitioned between ethyl acetate (100 mL) and brine (100 mL)
  2. washthe organic phase was washed with brine (2×100 mL)
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. customthe solvent evaporated
  6. customThe resulting gum was purified by silica gel chromatography
  7. washeluting with 47.5:47.5:5 isohexane
  8. additionThe fractions containing product
  9. additiontoluene (200 mL) was added
  10. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-9072cdb2dcc84300b9d22d26e72d8114
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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