Diisopropylethylamine → 4-(3-{(R)-3-[1-(4-hydroxy-phenyl)-2-methoxycarbonyl-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 526317Notes

Reaction equation

HRID 526317 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](O)=[O:25])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:51][O:52][C:53](=[O:64])[CH2:54][CH:55]([NH2:63])[C:56]1[CH:61]=[CH:60][C:59]([OH:62])=[CH:58][CH:57]=1.C(N(C(C)C)C(C)C)C>CN(C)C=O.O>[OH:62][C:59]1[CH:60]=[CH:61][C:56]([CH:55]([NH:63][C:24]([C@@H:20]2[CH2:21][CH2:22][CH2:23][N:18]([C:16](=[O:17])[CH2:15][CH2:14][CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:9][CH2:10]3)[CH2:19]2)=[O:25])[CH2:54][C:53]([O:52][CH3:51])=[O:64])=[CH:57][CH:58]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 54408184(R)-1-(3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidinecarboxylic acid2×HCID 58961718Methyl 3-Amino-3-(4-hydroxyphenyl)propanoate

Product 1

HCID 712590204-(3-{(R)-3-[1-(4-hydroxy-phenyl)-2-methoxycarbonyl-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl esterYield 85.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

490.75 mg (1.33 mmol) (3R)-1-{3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propanoyl}piperidine-3-carboxylic acid (Bioorg. Med. Chem. 13 (2005) 4343-4352, Compound 10) were suspended in 8 ml N,N-dimethylformamide and cooled to 0° C. 0.545 g (1.43 mmol) HATU, a solution of 200.0 mg (1.0 mmol) 3-amino-3-(4-hydroxy-phenyl)-propionic acid methyl ester in 12 ml N,N-dimethylformamide and 0.53 ml (3.07 mmol) N-ethyl-diisopropylamine were added. The mixture was stirred at 0° C. for 5 minutes and at room temperature for 24 hours. 20 ml water were added and the mixture extracted with dichloromethane, washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuum. Chromatography over 28 g basic silica gel (dichloromethane/ethanol 100/0-95/5-90/10-80/20) gave 465 mg (83%) tert-butyl 4-[3-((3R)-3-{[1-(4-hydroxyphenyl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl)-3-oxopropyl]piperidine-1-carboxylate.

Workup

  1. extractionthe mixture extracted with dichloromethane
  2. washwashed with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-c8707850eee749d588bebe38f8ee57f9
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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