Triethylamine → HCID 18982836, compound

HRID 1464606Notes

Reaction equation

HRID 1464606 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 HCl, 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% 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 HCl, 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% ethyl acetate/hexane eluent)

Sources & evidence

ORD record
ord-e4deb6956fd142b69ba33ef7d8b7b74c
Source dataset
uspto-grants-1994_04
Patent number
US05306723

Reaction notes

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