4-Methylmorpholine → HCID 178501216, compound

HRID 1757010Notes

Reaction equation

HRID 1757010 reaction equation
[C:1]([CH:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)([OH:3])=O.Cl.[CH3:19][O:20][C:21]([C@H:23]1[CH2:28][CH2:27][C@H:26]([NH:29][CH2:30][CH2:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:25][CH2:24]1)=[O:22].ON1C2C=CC=CC=2N=N1.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.F[B-](F)(F)F.CN1CCOCC1>CN(C)C=O.C(=O)(O)[O-].[Na+]>[C:16]([C:13]1[CH:14]=[CH:15][C:10]([N:7]2[CH2:8][CH2:9][CH:4]([C:1]([N:29]([C@H:26]3[CH2:27][CH2:28][C@H:23]([C:21]([O:20][CH3:19])=[O:22])[CH2:24][CH2:25]3)[CH2:30][CH2:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:3])[CH2:5][CH2:6]2)=[CH:11][CH:12]=1)#[N:17]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 193914381-(4-Cyanophenyl)piperidine-4-carboxylic acidHCID 178501215HCID 178501215, compound

Product 1

HCID 178501216HCID 178501216, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 1.37 g of 4-carboxy-1-(4-cyanophenyl)-piperidine, 1.85 g of N-[trans-4-(methoxycarbonyl)-cyclohexyl]-N-(3-phenylpropyl)-amine-hydrochloride, 0.88 g of 1-hydroxy-(1H)-benzotriazole, 2.1 g of 2-[(1H)-benzotriazol-1-yl]-1,1,3,3-tetramethyl-uronium-tetrafluoroborate and 1.43 ml of N-methyl-morpholine in 40 ml of dimethylformamide is heated to 60° C. for 6 hours. After cooling, the mixture is diluted with sodium bicarbonate solution and the aqueous phase is extracted with ethyl acetate. The combined ethyl acetate phases are washed with dilute citric acid solution and then with a dilute sodium bicarbonate solution and dried and the solvent is removed under reduced pressure. The residue is chromatographed with methylene chloride and methylene chloride/methanol (8:2) over silica gel. Yield: 0.55 (19% of theory), Melting point: 145°-146° C.

Workup

  1. temperatureAfter cooling
  2. extractionthe aqueous phase is extracted with ethyl acetate
  3. washThe combined ethyl acetate phases are washed with dilute citric acid solution
  4. dry with materialwith a dilute sodium bicarbonate solution and dried
  5. customthe solvent is removed under reduced pressure
  6. customThe residue is chromatographed with methylene chloride and methylene chloride/methanol (8:2) over silica gel

Sources & evidence

ORD record
ord-c9bfc06ab3704181ba36c2b7c9d4a793
Source dataset
uspto-grants-1995_08
Patent number
US05442064

Reaction notes

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