Cesium carbonate → HCID 89442480, compound

HRID 2283944Notes

Reaction equation

HRID 2283944 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH2:20][CH2:21][N:22]3[CH2:25][CH2:24][CH2:23]3)[CH:16]=[C:17](Br)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][C:28]=1[CH3:36].C([O-])([O-])=O.[Cs+].[Cs+]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH2:20][CH2:21][N:22]3[CH2:25][CH2:24][CH2:23]3)[CH:16]=[C:17]([C:30]3[CH:31]=[CH:32][C:27]([F:26])=[C:28]([CH3:36])[CH:29]=3)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2774580(4-Fluoro-3-methylphenyl)boronic acidHCID 89442949HCID 89442949, compound

Product 1

HCID 89442480HCID 89442480, compoundYield 99.4%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of 4-[1-(2-Azetidin-1-yl-ethyl)-4-bromo-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (8800.00 mg; 21.29 mmol; 1.00 eq.), 4-fluoro-3-methylphenylboronic acid (3932.91 mg; 25.55 mmol; 1.20 eq.) and Cs2CO3 (13872.97 mg; 42.58 mmol; 2.00 eq.) in doxane (80 ml) and water (8 ml) was purged by argon for 10 min, then Bis(tri-t-butylphosphine)palladium(0) (435.20 mg; 0.85 mmol; 0.04 eq.) was added under argon flow and purged by argon for 1 min. The resulting mixture was stirred at 50 C overnight. The reaction solution was diluted with ethyl acetate 250 ml, washed with brine-100 ml×2. The organic layer was dried and concentrated to afford the crude product which is purified by biotage Ki-Sil column to yield 4-[1-(2-azetidin-1-yl-ethyl)-4-(4-fluoro-3-methyl-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (9370.00 mg; 99% yield).

Workup

  1. customwas purged by argon for 10 min
  2. custompurged by argon for 1 min
  3. additionThe reaction solution was diluted with ethyl acetate 250 ml
  4. washwashed with brine-100 ml×2
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customto afford the crude product which
  8. customis purified by biotage Ki-Sil column

Sources & evidence

ORD record
ord-e82f7700de864bf3accc2134903d5e4a
Source dataset
uspto-grants-2015_09
Patent number
US09145392B2

Reaction notes

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