4-Methylmorpholine → HCID 54543994, compound

HRID 1978836Notes

Reaction equation

HRID 1978836 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:14][CH3:15])=[C:6]([C:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH:9]=2)[CH:7]=1.[CH3:16][N:17]([CH:25]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:26](O)=[O:27])[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C)C=O.O.CCOC(C)=O>[C:21]([O:20][C:18](=[O:19])[N:17]([C@H:25]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:26]([N:11]1[CH2:12][CH2:13][C:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:14][CH3:15])=[CH:9][CH2:10]1)=[O:27])[CH3:16])([CH3:24])([CH3:22])[CH3:23]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 52406092-{[(Tert-butoxy)carbonyl](methyl)amino}-3-phenylpropanoic acidHCID 18679661HCID 18679661, compound2×

Product 1

HCID 54543994HCID 54543994, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

The crude product of 4-(5-fluoro-2-methoxy-phenyl)-1,2,5,6-tetrahydropyridine (0.49 g, 2.4 mmole) (Intermediate 9) was dissolved in N,N-dimethylformamide (10 mL) at 0° C., and the resulting solution treated with 2-[N-methyl-N-(tert-butoxycarbonyl)-amino]-3-phenyl-propionic acid (0.73 g, 2.6 mmole) in a minimal amount of DMF, DAEC (0.50 g, 2.6 mmole), HOBT (0.42 g, 3.1 mmole) and NMM (0.40 mL, 3.6 mmole). The mixture was stirred overnight, and was diluted with water (50 mL) and EtOAc (50 mL). The layers were separated and the organic layer was washed with HCl (1N), saturated NaHCO3, and the combined aqueous washings were extracted three times with EtOAc (3×25 mL). The combined organic layers were dried over Na2SO4 and concentrated to afford (R)-{1-benzyl-2-[4-(5-fluoro-2-methoxy-phenyl)-1,2,5,6-tetrahydropyridin-1-yl]-2-oxo-ethyl}-methyl-carbamic acid tert-butyl ester as a yellow oil.

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with HCl (1N), saturated NaHCO3
  3. extractionthe combined aqueous washings were extracted three times with EtOAc (3×25 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a39bf0fb5f224c91879f63bd1076c7b9
Source dataset
uspto-grants-2001_05
Patent number
US06239126B1

Reaction notes

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