4-Methylmorpholine → HCID 11582801, compound

HRID 908958Notes

Reaction equation

HRID 908958 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1.[CH3:33][N:34]([CH3:52])[C:35]1([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[CH:46]=2)[CH2:40][CH2:39][C:38](=[CH:41][C:42](O)=[O:43])[CH2:37][CH2:36]1.[OH-].[Na+]>CN(C)C=O.O>[CH3:52][N:34]([CH3:33])[C:35]1([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[CH:46]=2)[CH2:40][CH2:39][C:38](=[CH:41][C:42]([NH:10][CH2:9][CH2:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:43])[CH2:37][CH2:36]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 162593-PhenylpropylamineHCID 67386283[4-Dimethylamino-4-(3-fluoro-phenyl)-cyclohexylidene]acetic acid

Product 1

HCID 11582801HCID 11582801, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

3-phenylpropylamine (768 mg, 5.68 mmol), N-methylmorpholine (1.15 g, 11.36 mmol) and dicyclohexylcarbodiimide (2.34 g, 11.36 mmol) were added to a solution of [4-dimethylamino-4-(3-fluoro-phenyl)-cyclohexylidene]acetic acid (1.5 g, 5.68 mmol) in dry dimethylformamide (35 ml) under argon and the mixture was stirred at RT for 3 d. The urea which had precipitated out was separated off and the filtrate was introduced into a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml). Still further urea thereby precipitated out and was separated off. The aqueous phase was diluted with water (300 ml), 5 M sodium hydroxide solution (7 ml, 35 mmol) was added and the mixture was stored at 5° C. for 20 h. The crude product thereby precipitated out as a beige-coloured solid (2.16 g). After chromatography on silica gel G [100 g; EtOAc/MeOH (10:1)], the amide was obtained in a yield of 29% (648.5 mg) with an m.p. of 129-131° C.

Workup

  1. customThe urea which had precipitated out
  2. customwas separated off
  3. additionthe filtrate was introduced into a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml)
  4. customStill further urea thereby precipitated out and
  5. customwas separated off
  6. additionwas added
  7. waitthe mixture was stored at 5° C. for 20 h
  8. customThe crude product thereby precipitated out as a beige-coloured solid (2.16 g)

Sources & evidence

ORD record
ord-96fe3e817ef7482d85716aea86e885fa
Source dataset
uspto-grants-2011_09
Patent number
US08017630B2

Reaction notes

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