Triethylamine → (2R,4S)-N-[1-(3,5-Bis-trifluoromethyl-benzoyl)-2-benzyl-piperidin-4-yl]-quinoline-4-carboxamide

HRID 1738912Notes

Reaction equation

HRID 1738912 reaction equation
O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.[CH2:16]([C@@H:23]1[CH2:28][C@@H:27]([NH2:29])[CH2:26][CH2:25][N:24]1[C:30](=[O:45])[C:31]1[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[C:33]([C:41]([F:44])([F:43])[F:42])[CH:32]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[N:46]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[C:49]([C:56](O)=[O:57])=[CH:48][CH:47]=1.C(N(CC)CC)C>C(Cl)Cl>[F:43][C:41]([F:44])([F:42])[C:33]1[CH:32]=[C:31]([CH:36]=[C:35]([C:37]([F:38])([F:39])[F:40])[CH:34]=1)[C:30]([N:24]1[CH2:25][CH2:26][C@H:27]([NH:29][C:56]([C:49]2[C:50]3[C:55](=[CH:54][CH:53]=[CH:52][CH:51]=3)[N:46]=[CH:47][CH:48]=2)=[O:57])[CH2:28][C@H:23]1[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)=[O:45]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 102434-Quinolinecarboxylic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 22869971(2R,4S)-2-benzyl-1-(3,5-bis-(trifluoromethyl)benzoyl)-4-piperidinamine

Product 1

HCID 18392944(2R,4S)-N-[1-(3,5-Bis-trifluoromethyl-benzoyl)-2-benzyl-piperidin-4-yl]-quinoline-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2.95 g (11.6 mmol) of bis(2-oxo-3-oxazolidinyl)phosphinic acid chloride are added at 0° C. to a solution of 4.16 g (9.67 mmol) of (2R,4S)-2-benzyl-1-(3,5-bis-trifluoromethyl-benzoyl)-4-piperidineamine [EP 532 456 A1, Example 38 f], 1.84 g (10.6 mmol) of quinoline4-carboxylic acid and 3 ml (21.3 mmol) of triethylamine in 30 ml of methylene chloride and the ice bath is removed after 10 minutes. The reaction mixture is stirred for 4 hours at room temperature and then diluted with methylene chloride. The organic phase is extracted with aqueous 10% citric acid and with 1 N potassium carbonate solution, washed with brine, dried over magnesium sulfate and concentrated to dryness by evaporation. The crude product is chromatographed on silica gel with methylene chloride/acetone (7:3). The title compound is crystallised from methylene chloride/ether/hexane in the form of white crystals. M.p.: 187° C.; TLC: methylene chloride/acetone (7:3) Rf =0.48, FD-MS: M+ =585; [alpha]D=+9.9 (c=1, methylene chloride); analysis: calc.: C=63.59%, H=4.30%, N=7.18%, F=19.47%, found: C=63.50%, H=4.40%, N=7.16%, F=19.45%. ##STR15##

Workup

  1. customthe ice bath is removed after 10 minutes
  2. additiondiluted with methylene chloride
  3. extractionThe organic phase is extracted with aqueous 10% citric acid and with 1 N potassium carbonate solution
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated to dryness by evaporation
  7. customThe crude product is chromatographed on silica gel with methylene chloride/acetone (7:3)
  8. customThe title compound is crystallised from methylene chloride/ether/hexane in the form of white crystals

Sources & evidence

ORD record
ord-5f96a656d2334b08bcdb6e955222cc0f
Source dataset
uspto-grants-1999_10
Patent number
US05965562

Reaction notes

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