Sodium Carbonate → (2R,5S)-2-[4-(2-fluoro-5-hydroxy-phenyl)-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one

HRID 2207660Notes

Reaction equation

HRID 2207660 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@H:8]2[CH2:12][CH2:11][C@@:10]3([CH2:16][CH2:15][N:14]([CH3:17])[C:13]3=[O:18])[NH:9]2)[CH:3]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>CC#N.O.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:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:21]=1[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@H:8]2[CH2:12][CH2:11][C@@:10]3([CH2:16][CH2:15][N:14]([CH3:17])[C:13]3=[O:18])[NH:9]2)[CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 467394012-Fluoro-5-hydroxyphenylboronic acidHCID 89649068(2R,5S)-2-(4-bromo-2-pyridyl)-7-methyl-1,7-diazaspiro[4.4]nonan-6-one

Product 1

HCID 89649657(2R,5S)-2-[4-(2-fluoro-5-hydroxy-phenyl)-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-oneYield 77.9%

Reagents, catalysts & solvents 3

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (2R,5S)-2-(4-bromo-2-pyridyl)-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (which may be prepared as described in Description 4) (140 mg, 0.4513 mmol) in MeCN (1.5 mL) and water (0.3000 mL) in a Smith microwave vessel was added (2-fluoro-5-hydroxy-phenyl)boronic acid (0.0774 g, 0.4965 mmol), bis(triphenylphosphine)palladium (II) dichloride (0.0095 g, 0.0135 mmol) and sodium carbonate (0.0957 g, 0.9027 mmol). The reaction vessel was sealed and purged with nitrogen. The reaction mixture was heated by microwave at 100° C. for 40 min. The reaction mixture was treated with water and was extracted with DCM twice and the organic layers were collected by passing down a PhaseSep cartridge. Evaporation of solvents gave an amber oil, It was further purified by silica gel chromatography (11 g KPNH silica cartridge) eluting with ethyl acetate in iso-hexane (20-100%) followed by methanol in ethyl acetate (0-18%) to give the desired product (2R,5S)-2-[4-(2-fluoro-5-hydroxy-phenyl)-2-pyridyl]-7-methyl-1,7-diazaspiro[4.4]nonan-6-one (D134) (0.1200 g, 0.3515 mmol, 77.9% yield) as cream solid;

Workup

  1. customThe reaction vessel was sealed
  2. custompurged with nitrogen
  3. additionThe reaction mixture was treated with water
  4. extractionwas extracted with DCM twice
  5. customthe organic layers were collected
  6. customEvaporation of solvents
  7. customgave an amber oil, It
  8. customwas further purified by silica gel chromatography (11 g KPNH silica cartridge)
  9. washeluting with ethyl acetate in iso-hexane (20-100%)

Sources & evidence

ORD record
ord-305f3995c6794fc0b81a71271f0d56f4
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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