Binap, (A+-)- → 1,1-Dimethylethyl 4-(6-chloro-4-fluoro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

HRID 447760Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([F:9])[C:3]=1[NH:10][C:11]([NH:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[O:12].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:8][C:6]1[CH:5]=[C:4]([F:9])[C:3]2[NH:10][C:11](=[O:12])[N:13]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[C:2]=2[CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Under an argon atmosphere, 1,1-dimethylethyl 4-({[(2-bromo-4-chloro-6 fluorophenyl)amino]carbonyl}amino)-1-piperidinecarboxylate (D7) (1.09 mmol, 0.493 g), 1,4-dioxane (4.4 ml), Pd2 dba3 (0.05 eq., 0.054 mmol, 50 mg), BINAP (0.055 eq., 0.059 mmol, 37 mg), NatBuO (1.5 eq., 1.63 mmol, 157 mg) were mixed together and heated to 80° C. under argon for 4 days. The reaction mixture was cooled to room temperature, quenched with water and the aqueous solution obtained was extracted with ethyl acetate. The solvent was evaporated and the crude was purified by MDAP. Fractions were collected and the solvent evaporated to yield the title compound, 15 mg, 3%, M+-H=368.

Workup

temperatureThe reaction mixture was cooled to room temperature
customquenched with water
customthe aqueous solution obtained
extractionwas extracted with ethyl acetate
customThe solvent was evaporated
customthe crude was purified by MDAP
customFractions were collected
customthe solvent evaporated

Sources & evidence

ORD record: ord-9c5bc89a15ee49d6b932fce5d641b7ca
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481566B2

Reaction notes

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