Diethylaluminum chloride → HCID 15512823, compound

HRID 2268074Notes

Reaction equation

HRID 2268074 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:14][CH3:15])=[C:6]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]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].CC[Al](Cl)CC.C1C=CC2N(O)N=NC=2C=1.C[N+]1([O-])CCOCC1>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][CH:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:14][CH3:15])[CH2:9][CH2:10]1)=[O:27])[CH3:16])([CH3:24])([CH3:22])[CH3:23]

Participants

9

Reactant 5

HCID 7277Diethylaluminum chlorideHCID 757711-HydroxybenzotriazoleHCID 82029Methyl morpholine oxideHCID 52406092-{[(Tert-butoxy)carbonyl](methyl)amino}-3-phenylpropanoic acidHCID 155128224-(5-Fluoro-2-methoxyphenyl)piperidine

Product 1

HCID 15512823HCID 15512823, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

The above product of 4-(5-fluoro-2-methoxy-phenyl)-piperidine was dissolved in N,N-dimethylformamide (10 mL) at 0° C. To the resulting solution, 0.70 g (2.5 mmole) of 2-[N-methyl-N-(tert-butoxycarbonyl)-amino]-3-phenyl-propionic acid in a minimal amount of DMF was added, followed by DEAC (0.48 g, 2.5 mmole), HOBT (0.41 g, 2.5 mmole) and NMO (0.37 mL, 3.4 mmole) and the mixture was stirred overnight (the reaction temperature was slowly allowed to warm up to room temperature). The reaction mixture was diluted with water (50 mL) and EtOAc (50 mL) and the layers separated. The aqueous layer was washed with HCl (1N), saturated NaHCO3, and the combined aqueous layers were extracted three times with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. Flash chromatography, gradient elution with 1:4 EtOAc-hexane to 3:7 EtOAc-hexane to afford (R)-{1-benzyl-2-[4-(5-fluoro-2-methoxy-phenyl)-piperidin-1-yl]-2-oxo-ethyl}-methyl-carbamic acid tert-butyl ester as a yellow oil.

Workup

  1. customthe layers separated
  2. washThe aqueous layer was washed with HCl (1N), saturated NaHCO3
  3. extractionthe combined aqueous layers were extracted three times with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. washFlash chromatography, gradient elution with 1:4 EtOAc-hexane to 3:7 EtOAc-hexane

Sources & evidence

ORD record
ord-c07b0997120248319aa031265f7a9c06
Source dataset
uspto-grants-2001_12
Patent number
US06326381B1

Reaction notes

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