Cesium carbonate → HCID 89922979, compound

HRID 921962Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Br:11])[C:9]=1[Cl:10])[C:5]#[N:6].[NH2:12][C@@H:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][C@H:14]1[OH:23].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.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[Br:11][C:8]1[C:9]([Cl:10])=[C:2]([NH:12][C@@H:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][C@H:14]2[OH:23])[CH:3]=[C:4]([C:5]#[N:6])[CH:7]=1

Participants

Conditions

Temperature: 105 °C

Procedure

A mixture of 3,5-dibromo-4-chlorobenzonitrile (160 mg, 0.542 mmol), (3R,4R)-methyl 4-amino-3-hydroxypiperidine-1-carboxylate (88 mg, 0.505 mmol), Pd2(dba)3 (69.4 mg, 0.076 mmol), BINAP (47.2 mg, 0.076 mmol), and Cs2CO3 (494 mg, 1.516 mmol) in a dry microwave vial was flushed with nitrogen. Toluene (3.7 mL) was added and the vial was sealed and heated at 105° C. for 4 hours. The reaction was partitioned between EtOAc and water. The organic phase was washed with brine and dried with sodium sulfate. Removal of the solvent followed by silica gel chromatography eluting with hexane containing 20% to 50% EtOAc afforded (3R,4R)-methyl 4-((3-bromo-2-chloro-5-cyanophenyl)amino)-3-hydroxypiperidine-1-carboxylate (20 mg).

Workup

customwas flushed with nitrogen
additionToluene (3.7 mL) was added
customthe vial was sealed
customThe reaction was partitioned between EtOAc and water
washThe organic phase was washed with brine
dry with materialdried with sodium sulfate
customRemoval of the solvent
washeluting with hexane containing 20% to 50% EtOAc

Sources & evidence

ORD record: ord-9189d667a8084013b45c03d36a85b5cc
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273057B2

Reaction notes

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