Hydrochloric Acid → HCID 66611075, compound

HRID 2204720Notes

Reaction equation

HRID 2204720 reaction equation
Br[C:2]1[C:3]([C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:29])=[CH:4][C:5]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[C:6]([CH:18]=1)[C:7]([O:9]CC1C=CC(F)=CC=1)=[O:8].[CH3:36][N:37]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[N:38]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Li+].Cl>COCCOC.O.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.O1CCCC1>[F:27][C:24]1[CH:23]=[CH:22][C:21]([CH2:20][O:19][C:5]2[CH:4]=[C:3]([C:28]([N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)=[O:29])[C:2]([C:40]3[CH:39]=[N:38][N:37]([CH3:36])[CH:41]=3)=[CH:18][C:6]=2[C:7]([OH:9])=[O:8])=[CH:26][CH:25]=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 66611702HCID 66611702, compound

Product 1

HCID 66611075HCID 66611075, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent4×HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 4-fluorobenzyl 5-bromo-2-((4-fluorobenzyl)oxy)-4-(morpholine-4-carbonyl)benzoate (380 mg, 0.696 mmol) (may be prepared as described in description D19) in 1,2-Dimethoxyethane (DME) (10 mL)/Water (1.00 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (217 mg, 1.043 mmol), Tetrakis (48.2 mg, 0.042 mmol), tripotassium phosphate (295 mg, 1.391 mmol). The vial was sealed and heated to 130° C. for 25 min. Mixture was diluted with water (50 ml) and extracted with ethyl acetate (3×50 ml), the organics were combined, dried (MgSO4) and evaporated on a buchi under reduced pressure. No attempt was made to purify this intermediate it was taken up into a mixture of Tetrahydrofuran (THF) (10.00 mL)/Water (1.00 mL) and lithium hydroxide (33.3 mg, 1.391 mmol) was added. The mixture was then heated to 80° C. for 3 hrs. The mixture on cooling was diluted with water (50 ml) and acidified to pH2 using 2M aqueous HCl. The solid formed was filtered off, washed with water (2×20 ml) and dried in air under vacuum to give the title compound as an off white solid.

Workup

  1. customThe vial was sealed
  2. extractionextracted with ethyl acetate (3×50 ml)
  3. dry with materialdried (MgSO4)
  4. customevaporated on a buchi under reduced pressure
  5. customto purify this intermediate it
  6. additionwas added
  7. temperatureThe mixture was then heated to 80° C. for 3 hrs
  8. temperatureThe mixture on cooling
  9. customThe solid formed
  10. filtrationwas filtered off
  11. washwashed with water (2×20 ml)
  12. customdried in air under vacuum

Sources & evidence

ORD record
ord-e72b337f3ec94ad480992e213a391e78
Source dataset
uspto-grants-2016_06
Patent number
US09365551B2

Reaction notes

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