Dichloromethane → HCID 58495588, compound

HRID 1190987

Reaction equation

HRID 1190987 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13](Cl)=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:17]1([CH:23]=[CH:24]B(O)O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[N:12][C:13](/[CH:24]=[CH:23]/[CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 41851492-Cyclohexylvinyl boronic acidHCID 15449580tert-Butyl [(6-chloropyridin-3-yl)methyl]carbamate

Product 1

HCID 58495588HCID 58495588, compoundYield 70.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Combine 3-(tert-butoxycarbonylamino-methyl)-6-chloropyridine (1.42 g, 5.85 mmol), 2-cyclohexylvinyl boronic acid (1.35 g, 8.78 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with DCM (239 mg, 0.293 mmol), and 2M aqueous Na2CO3 (9.65 mL, 19.2 mmol) in 1,4-dioxane (60 mL). Purge the resulting solution with nitrogen for 5 min and heat at 90° C. overnight. Cool the reaction mixture to room temperature and partition the mixture between EtOAc and water. Separate the aqueous phase and extract twice with EtOAc. Dry the combined organic extracts over MgSO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (120 g, pre-packed cartridge) eluting stepwise with hexane/EtOAc (1:0 over 5 min, 49:1 over 5 min, 19:1 over 5 min, 9:1 over 5 min and 85:15 over 5 min; 50 mL/min) to obtain the desired intermediate (1.3 g, 70%). MS (APCI+) m/z: 317 (M+H)+.

Workup

  1. customPurge the resulting solution with nitrogen for 5 min
  2. temperatureCool the reaction mixture to room temperature
  3. custompartition the mixture between EtOAc and water
  4. customSeparate the aqueous phase
  5. extractionextract twice with EtOAc
  6. dry with materialDry the combined organic extracts over MgSO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customPurify by chromatography on silica gel (120 g, pre-packed cartridge)
  10. washeluting stepwise with hexane/EtOAc (1:0 over 5 min, 49:1 over 5 min, 19:1 over 5 min, 9:1 over 5 min and 85:15 over 5 min; 50 mL/min)

Sources & evidence

ORD record
ord-9424f586a7394a96a3c87a41a5d7c978
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Linked notes

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