Sodium Bicarbonate → HCID 60141063, compound

HRID 1946928Notes

Reaction equation

HRID 1946928 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([CH3:15])[CH2:13][O:12][CH2:11][C:10]([NH2:14])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])O.[Na+].[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1B(O)O>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>[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2([CH3:15])[CH2:13][O:12][CH2:11][C:10]([NH2:14])=[N:9]2)[CH:3]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 58155185HCID 58155185, compound

Product 1

HCID 60141063HCID 60141063, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A degassed solution of (RS)-5-(3-bromo-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (intermediate XII-1) (100 mg, 0.37 mmol) in 1,2-dimethoxyethane was treated with tetrakis(triphenylphosphine)palladium(0) (42.7 mg, 0.037 mmol), then purged again with argon for 15 minutes. Thereafter, a solution of sodium hydrogencarbonate (1 M, 0.5 ml) and 2,4-difluoro-benzene-boronic acid (116.5 g, 0.74 mmol) were added. The tube was sealed and the mixture heated to 100° C. for 3 hours. For the workup, the reaction mixture was filtered through Celite®, then extracted with dichloromethane (2×15 ml). The combined organic layers were evaporated and the residue was repeatedly (3×) purified by chromatography on a silica-amine phase. The (RS)-5-(2′,4′-difluoro-biphenyl-3-yl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine was obtained as an off-white solid (20 mg, 18% of theory). MS (ISP): m/z=303.4 [M+H]+.

Workup

  1. custompurged again with argon for 15 minutes
  2. customThe tube was sealed
  3. filtrationFor the workup, the reaction mixture was filtered through Celite®
  4. extractionextracted with dichloromethane (2×15 ml)
  5. customThe combined organic layers were evaporated
  6. custompurified by chromatography on a silica-amine phase

Sources & evidence

ORD record
ord-7c16ee1da7f2436f870aee09bada9e56
Source dataset
uspto-grants-2013_03
Patent number
US08399459B2

Reaction notes

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