Cesium carbonate → Ammonia

HRID 2204687Notes

Reaction equation

HRID 2204687 reaction equation
Br[C:2]1[C:11]([CH2:12][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([OH:19])[CH:3]=1.[CH3:20][N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+].[F:49][C:50]1[CH:57]=[CH:56][C:53]([CH2:54]Br)=[CH:52][CH:51]=1>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C.O>[NH3:13].[F:49][C:50]1[CH:57]=[CH:56][C:53]([CH2:54][O:19][C:4]2[CH:3]=[C:2]([C:24]3[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=3)[C:11]([CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:10][C:5]=2[C:6]([O:8][CH3:9])=[O:7])=[CH:52][CH:51]=1

Participants

11

Reactant 5

HCID 10796Cesium carbonateHCID 62657Potassium Phosphate, TribasicHCID 680214-Fluorobenzyl bromideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 66611279HCID 66611279, compound

Product 2

HCID 222AmmoniaYield 10%HCID 66611435HCID 66611435, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 4-bromo-2-hydroxy-5-(4-morpholinylmethyl)benzoate (may be prepared as described in Description 17; 250 mg, 0.76 mmol) in 1,2-dimethoxyethane (3 ml) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (189 mg, 0.91 mmol), tripotassium phosphate (321 mg, 1.51 mmol), and Pd(Ph3P)4 (52.5 mg, 0.05 mmol). The reaction was heated at 120° C. for one hour, cooled and the solvent removed in vacuo. The residue was redissolved in N,N-dimethylformamide (4 ml) and cesium carbonate (493 mg, 1.15 mmol) and 4-fluorobenzyl bromide (0.11 ml, 0.91 mmol) were added and the mixture heated at 40° C. for 3 hours. Water (10 ml) and ethyl acetate (15 ml) were added and the organic layer was separated and washed further with water (2×10 ml), dried (MgSO4) and the solvent removed in vacuo. Purification by column chromatography (SiO2; (solute, 10% 7M NH3 in methanol/dichloromethane) yielded the title compound as a gum. 333 mg.

Workup

  1. temperaturecooled
  2. customthe solvent removed in vacuo
  3. dissolutionThe residue was redissolved in N,N-dimethylformamide (4 ml)
  4. temperaturethe mixture heated at 40° C. for 3 hours
  5. customthe organic layer was separated
  6. washwashed further with water (2×10 ml)
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed in vacuo
  9. customPurification by column chromatography (SiO2

Sources & evidence

ORD record
ord-700c76748cd848699c7a6e20afbca642
Source dataset
uspto-grants-2016_06
Patent number
US09365551B2

Reaction notes

Loading…