Hydrochloric Acid → 5-(1-Methyl-1H-pyrazol-4-yl)-4-(4-morpholinylcarbonyl)-2-[(phenylmethyl)oxy]benzoic acid

HRID 2204691Notes

Reaction equation

HRID 2204691 reaction equation
Br[C:2]1[C:3]([C:26]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:27])=[CH:4][C:5]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:6]([CH:17]=1)[C:7]([O:9]CC1C=CC=CC=1)=[O:8].[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Li+].Cl>COCCOC.O1CCCC1.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.O>[CH3:34][N:35]1[CH:39]=[C:38]([C:2]2[C:3]([C:26]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[O:27])=[CH:4][C:5]([O:18][CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[C:6]([CH:17]=2)[C:7]([OH:9])=[O:8])[CH:37]=[N:36]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 66611922Phenylmethyl 5-bromo-4-(4-morpholinylcarbonyl)-2-[(phenylmethyl)oxy]benzoate

Product 1

HCID 666111175-(1-Methyl-1H-pyrazol-4-yl)-4-(4-morpholinylcarbonyl)-2-[(phenylmethyl)oxy]benzoic acid

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of phenylmethyl 5-bromo-4-(4-morpholinylcarbonyl)-2-[(phenylmethyl)oxy]benzoate (may be prepared as described in Description 25; 730 mg, 1.430 mmol) in 1,2-dimethoxyethane (6 ml) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (357 mg, 1.72 mmol), tripotassium phosphate (607 mg, 2.86 mmol) and Pd(Ph3P)4 (99 mg, 0.09 mmol) followed by water (0.5 ml). The mixture was heated in a microwave at 130° C. for 90 minutes, cooled and the solvent removed in vacuo. Purification by column chromatography (SiO2; 1:1 ethyl acetate/cyclohexane to 10% 7M NH3 in methanol/dichloromethane) gave the intermediate. To a solution of this intermediate in tetrahydrofuran (4 ml) was added lithium hydroxide (103 mg, 4.29 mmol) and water (0.5 ml). The solution was stirred for 18 hours before neutralising with 2M hydrochloric acid (2.15 ml, 4.29 mmol). The solvent removed in vacuo to give the product as a solid. 603 mg.

Workup

  1. temperaturecooled
  2. customthe solvent removed in vacuo
  3. customPurification by column chromatography (SiO2; 1:1 ethyl acetate/cyclohexane to 10% 7M NH3 in methanol/dichloromethane)
  4. customgave the intermediate
  5. customThe solvent removed in vacuo

Sources & evidence

ORD record
ord-b6c49c837baf45298be32aafc5af59bb
Source dataset
uspto-grants-2016_06
Patent number
US09365551B2

Reaction notes

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