1,2-Dimethoxyethane → Tert-butyl({6-chloro-4-[4-chloro-2-(2,6-difluorobenzoyl)phenyl]pyridin-3-yl}-methyl)carbamate

HRID 2237398Notes

Reaction equation

HRID 2237398 reaction equation
COCCOC.[Cl:7][C:8]1[CH:9]=[CH:10][C:11](I)=[C:12]([C:14]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=2[F:23])=[O:15])[CH:13]=1.[C:25]([O:29][C:30]([NH:32][CH2:33][C:34]1[C:35](B(O)O)=[CH:36][C:37]([Cl:40])=[N:38][CH:39]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[Na+].[Na+]>O.C(Cl)Cl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:25]([O:29][C:30](=[O:31])[NH:32][CH2:33][C:34]1[CH:39]=[N:38][C:37]([Cl:40])=[CH:36][C:35]=1[C:11]1[CH:10]=[CH:9][C:8]([Cl:7])=[CH:13][C:12]=1[C:14](=[O:15])[C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[F:23])([CH3:28])([CH3:26])[CH3:27]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 46835488(5-Chloro-2-iodophenyl)(2,6-difluorophenyl)methanoneHCID 59302622(5-{[(Tert-butoxy-carbonyl)amino]methyl}-2-chloropyridin-4yl)boronic acid

Product 1

HCID 59302624Tert-butyl({6-chloro-4-[4-chloro-2-(2,6-difluorobenzoyl)phenyl]pyridin-3-yl}-methyl)carbamateYield 24%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Into a 50-mL single-necked round-bottom flask was added 1,2-dimethoxy-ethane (10 mL). The solvent was purged with nitrogen, then tetrakis(triphenylphosphine)-palladium(0) (80.7 mg, 0.07 mmol) and (5-chloro-2-iodo-phenyl)-(2,6-difluoro-phenyl)-methanone (528 mg, 1.40 mmol) were added. The mixture was stirred under an atmosphere of nitrogen for 15 minutes, then (5-{[(tert-butoxycarbonyl)amino]methyl}-2-chloropyridin-4-yl)boronic acid (600.0 mg, 2.09 mmol) and 2.00 M sodium carbonate in water (1.40 mL) were added and the mixture was heated to reflux and allowed to stir 5 hours. The reaction was then cooled to room temperature and allowed to sit overnight. The reaction was diluted with methylene chloride (30 mL) and then transferred to a separatory funnel and was washed with water (2×30 mL). The organic portion was dried over sodium sulfate, filtered, and concentrated to provide the crude product as an orange oil. The crude product was purified by column chromatography on silica gel (elution gradient from dichloromethane to 15% ethyl acetate/dichloromethane) to yield 165 mg (24%) tert-butyl({6-chloro-4-[4-chloro-2-(2,6-difluorobenzoyl)phenyl]pyridin-3-yl}methyl)carbamate as an amber glass/solid. The product structure was confirmed by NMR and MS.

Workup

  1. customThe solvent was purged with nitrogen
  2. temperaturethe mixture was heated
  3. temperatureto reflux
  4. stirringto stir 5 hours
  5. waitto sit overnight
  6. customtransferred to a separatory funnel
  7. washwas washed with water (2×30 mL)
  8. dry with materialThe organic portion was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto provide the crude product as an orange oil
  12. customThe crude product was purified by column chromatography on silica gel (elution gradient from dichloromethane to 15% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-2786deb297834bad87edcfb6fa3176f0
Source dataset
uspto-grants-2010_05
Patent number
US07718648B2

Reaction notes

Loading…