Sodium Carbonate → HCID 89649221, compound

HRID 2207602Notes

Reaction equation

HRID 2207602 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH2:12][CH2:11][C@@:10]3([CH2:16][CH2:15][NH:14][C:13]3=[O:17])[N:9]=2)[CH:3]=1.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.ClCCl.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:18][C:19]([F:30])([F:29])[C:20]1[CH:25]=[CH:24][C:23]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([C:8]3[CH2:12][CH2:11][C@@:10]4([CH2:16][CH2:15][NH:14][C:13]4=[O:17])[N:9]=3)[CH:3]=2)=[CH:22][CH:21]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 89648923HCID 89648923, compound

Product 1

HCID 89649221HCID 89649221, compoundYield 74.1%

Reagents, catalysts & solvents 4

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (5S)-2-(4-bromo-2-pyridyl)-1,7-diazaspiro[4.4]non-1-en-6-one (which may be prepared as described in Description 19) (200 mg, 0.6800 mmol) in 1,2-dimethoxyethane (3 mL) and water (1 mL) was added [4-(trifluoromethyl)phenyl]-boronic acid (142.05 mg, 0.7500 mmol) and sodium carbonate (216.2 mg, 2.04 mmol). The reaction mixture was degassed with nitrogen and then treated with bis(triphenylphosphine)palladium (II) dichloride (23.86 mg, 0.0300 mmol). The reaction mixture was heated in the microwave at 120° C. for 50 minutes then cooled and diluted with dichloromethane and water. After separation of the layers, the aqueous phase was re-extracted with dichloromethane and the combined organic phases passed through a hydrophobic frit. The solvent was evaporated and the residue purified by silica gel chromatography eluting with 0-20% methanol in ethyl acetate to give (5S)-2-[4-[4-(trifluoromethyl)-phenyl]-2-pyridyl]-1,7-diazaspiro[4.4]non-1-en-6-one (D20) as a pale yellow solid (181 mg);

Workup

  1. customThe reaction mixture was degassed with nitrogen
  2. temperaturethen cooled
  3. customAfter separation of the layers
  4. extractionthe aqueous phase was re-extracted with dichloromethane
  5. customThe solvent was evaporated
  6. customthe residue purified by silica gel chromatography
  7. washeluting with 0-20% methanol in ethyl acetate

Sources & evidence

ORD record
ord-9ff5da1deafc4468906a1acb1a492258
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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