4-Methylmorpholine → HCID 11647294, compound

HRID 908952Notes

Reaction equation

HRID 908952 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.[CH3:18][N:19]([CH3:37])[C:20]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:25][CH2:24][C:23]([CH2:27][C:28](O)=[O:29])(O)[CH2:22][CH2:21]1.C1(N=C=NC2CCCCC2)CCCCC1.[OH-].[Na+]>O.CN(C)C=O>[CH3:37][N:19]([CH3:18])[C:20]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:25][CH2:24][C:23](=[CH:27][C:28]([NH:10][CH2:9][CH2:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:29])[CH2:22][CH2:21]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 162593-PhenylpropylamineHCID 67386014HCID 67386014, compound

Product 1

HCID 11647294HCID 11647294, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-phenylpropylamine (270 mg, 2.0 mmol) and N-methylmorpholine (0.444 ml, 4.0 mmol) were added to a solution of (4-dimethylamino-1-hydroxy-4-pyridin-2-yl-cyclohexyl)acetic acid (556 mg, 2.0 mmol) in abs. dimethylformamide (30 ml) under argon. The solution was cooled to 0° C., dicyclohexylcarbodiimide (825 mg, 4.0 mmol) was added and the mixture was stirred at RT for 5 d. Working up of the mixture was carried out by separating off the urea which had precipitated out and introducing the filtrate 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 16 h. The crude product thereby precipitated out as a beige-coloured oily compound (22.8 mg, 30%). After chromatography on silica gel (40 g) with EA/methanol (4:1), the amide was obtained as a beige-coloured oil in a yield of 27% (203 mg).

Workup

  1. customby separating off the urea which
  2. customhad precipitated out
  3. additionintroducing the filtrate
  4. additioninto a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml)
  5. customStill further urea thereby precipitated out and
  6. customwas separated off
  7. additionwas added
  8. waitthe mixture was stored at 5° C. for 16 h
  9. customThe crude product thereby precipitated out as a beige-coloured oily compound (22.8 mg, 30%)

Sources & evidence

ORD record
ord-e3680564e9bb4874bc59b80348411c04
Source dataset
uspto-grants-2011_09
Patent number
US08017630B2

Reaction notes

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