Triethylamine → HCID 18982836, compound

HRID 1440204Notes

Reaction equation

HRID 1440204 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:12](=[O:16])[CH:13](Cl)[CH3:14])[CH:5]=[C:6]2[C:10]=1[NH:9][C:8](=[O:11])[CH2:7]2.[OH:17][C:18]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.C(N(CC)CC)C.[Li+].[Cl-]>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([C:12](=[O:16])[CH:13]([N:21]2[CH2:22][CH2:23][C:18]([OH:17])([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:19][CH2:20]2)[CH3:14])[CH:5]=[C:6]2[C:10]=1[NH:9][C:8](=[O:11])[CH2:7]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 963874-Phenylpiperidin-4-olHCID 433294Lithium ChlorideHCID 18982834HCID 18982834, compound

Product 1

HCID 18982836HCID 18982836, compoundYield 36.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 7-fluoro-5-(2-chloropropionyl)-2(1H,3H)-indolone (1.0 g, 4.14 mmol), 4-hydroxy-4-phenylpiperidine (0.74 g, 4.17 mmol) and triethylamine (1.2 ml, 8.6 mmol) in anhydrous dimethylformamide was heated to between 70 and 90° C. for 3 hours. The mixture was poured into 1N aqueous LiCl and extracted with two portions of ethyl acetate. The combined organic phase was washed with 1N HCI, water and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated to 1.6 g of a reddish solid. The crude product was purified by flash chromatography on silica gel (2×4 inches {50×100 mm}, 50% ethyl acetate/hexane eluent) to yield 0.58 g of the desired product. This product was further purified by recrystallization from acetonitrile/ether to give 0.2 g of light yellow solid; m.p. 197°-199.5° C. NMR (DMSO-d6) 11.25 (s, 1H), 7.90 (d, J=11.6 Hz, 1H), 7.82 (s, 1H), 7.42 (d, J=7.2 Hz, 2H), 7.28 (t, J=7.4 Hz, 2H), 7.17 (t, J=7.2 Hz, 1H), 4.76 (s, 1H), 4.25 (q, J=6.6 Hz, 1H), 3.66 (s, 2H), 2.88-2.63 (m, 2H), 2.60-2.55 (m, 1h), 2.49-2.38 (m, 1H), 1.88 (dt, J=12.2, 4.3 Hz, 1H), 1.77-1.49 (m, 3H), 1.16 (d, J=6.6 Hz, 3H). The mother liquors were rechromatographed to afford another 0.15 g of product for a total yield of 0.35 g (22%).

Workup

  1. temperaturewas heated to between 70 and 90° C. for 3 hours
  2. extractionextracted with two portions of ethyl acetate
  3. washThe combined organic phase was washed with 1N HCI, water and brine
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to 1.6 g of a reddish solid
  7. customThe crude product was purified by flash chromatography on silica gel (2×4 inches {50×100 mm}, 50% ethyl acetate/hexane eluent)

Sources & evidence

ORD record
ord-6773a1c223be42eab3b7f3b8d188b480
Source dataset
uspto-grants-1996_03
Patent number
US05498610

Reaction notes

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