Diisopropylethylamine → 2-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71850

Reaction equation

HRID 71850 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH2:15])[CH:10]=2)=[CH:5][CH:4]=1.[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][CH2:25][CH:24]1[C:28](O)=[O:29])=[O:22])([CH3:19])([CH3:18])[CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][CH2:25][CH:24]1[C:28](=[O:29])[NH:15][C:11]1[CH:10]=[C:9]([C:6]2[CH:5]=[CH:4][C:3]([Cl:2])=[CH:8][CH:7]=2)[CH:14]=[CH:13][CH:12]=1)=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2684721-[(Tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 441197194'-Chloro-[1,1'-biphenyl]-3-amine hydrochloride

Product 1

HCID 666205302-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 99.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4′-Chloro-biphenyl-3-ylamine hydrochloride (1 g, 4.16 mmol), Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.08 g, 5.00 mmol) and HATU (2.06 g, 5.41 mmol) were suspended in DMF (20 mL) and DIPEA (2.20 mL, 12.5 mmol) was added. The mixture was stirred for 16 hours before being diluted with ethyl acetate (250 mL) and washed with water and brine. The organic layer was dried over magnesium sulfate and concentrated. The crude residue was purified by silica column chromatography (25% to 45% EtOAc/hexanes) to provide 2-(4′-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.66 g, 99%).

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. concentrationconcentrated
  4. customThe crude residue was purified by silica column chromatography (25% to 45% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f1163d7e17a04d59aa4d5aceb6e24f23
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Linked notes

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