4-Methylmorpholine → HCID 11712509, compound

HRID 908956Notes

Reaction equation

HRID 908956 reaction equation
ON1C2C=CC=CC=2N=N1.[CH3:11][CH:12]([NH2:23])[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1.CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1.[CH3:46][N:47]([CH3:65])[C:48]1([C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([F:64])[CH:59]=2)[CH2:53][CH2:52][C:51](=[CH:54][C:55](O)=[O:56])[CH2:50][CH2:49]1.[OH-].[Na+]>CN(C)C=O.O>[CH3:65][N:47]([CH3:46])[C:48]1([C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([F:64])[CH:59]=2)[CH2:53][CH2:52][C:51](=[CH:54][C:55]([NH:23][CH:12]([CH3:11])[CH2:13][C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][CH:15]=2)=[O:56])[CH2:50][CH2:49]1

Participants

9

Reactant 6

HCID 79724-MethylmorpholineHCID 9287(+-)-alpha-MethyltryptamineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 67386283[4-Dimethylamino-4-(3-fluoro-phenyl)-cyclohexylidene]acetic acid

Product 1

HCID 11712509HCID 11712509, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

1-Hydroxybenzotriazole (1.43 g, 10.6 mmol), DL-α-methyltryptamine (923.3 mg, 5.3 mmol), N-methylmorpholine (1.07 g, 10.6 mmol) and dicyclohexylcarbodiimide (2.19 g, 10.6 mmol) were added to a solution of [4-dimethylamino-4-(3-fluoro-phenyl)-cyclohexylidene]acetic acid (1.4 g, 5.3 mmol) in dry dimethylformamide (50 ml) under argon and the mixture was stirred at RT for 6 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 20 h. The crude product thereby precipitated out as a yellow solid (1.2 g). The product was a mixture of the two diastereoisomer amides, which were separated by chromatography on silica gel G [100 g; EtOAc/MeOH (10:1)]. The less polar diastereoisomer was obtained in a yield of 410.6 mg (18%) with an m.p. of 163-166° C. and the more polar diastereoisomer was obtained in a yield of 249.3 mg (11%), as a colourless oil.

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 20 h
  9. customThe crude product thereby precipitated out as a yellow solid (1.2 g)
  10. additiona mixture of the two diastereoisomer amides, which
  11. customwere separated by chromatography on silica gel G [100 g; EtOAc/MeOH (10:1)]
  12. customThe less polar diastereoisomer was obtained in a yield of 410.6 mg (18%) with an m.p. of 163-166° C.
  13. customthe more polar diastereoisomer was obtained in a yield of 249.3 mg (11%), as a colourless oil

Sources & evidence

ORD record
ord-de44ed4b582d4352902654d3c67565ff
Source dataset
uspto-grants-2011_09
Patent number
US08017630B2

Reaction notes

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