Toluene → HCID 67218981, compound

HRID 1788289Notes

Reaction equation

HRID 1788289 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:35]2[CH:40]=[CH:39][C:38](Br)=[CH:37][CH:36]=2)([O:14][CH2:15][C:16]2[N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:19]3[CH:29]=[C:30]([F:34])[C:31]([F:33])=[CH:32][C:18]=3[N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:42]([C:44]1[CH:45]=[C:46](B(O)O)[CH:47]=[CH:48][CH:49]=1)#[N:43].C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.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.C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:35]2[CH:40]=[CH:39][C:38]([C:48]3[CH:47]=[CH:46][CH:45]=[C:44]([C:42]#[N:43])[CH:49]=3)=[CH:37][CH:36]=2)([O:14][CH2:15][C:16]2[N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:19]3[CH:29]=[C:30]([F:34])[C:31]([F:33])=[CH:32][C:18]=3[N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 57603242HCID 57603242, compound

Product 1

HCID 67218981HCID 67218981, compoundYield 34.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 0.116 g of 4-(4-bromo-phenyl)-4-[5,6-difluoro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester 61 (˜0.18 mmol, 1 eq), 0.032 g of 3-cyanophenylboronic acid (0.215 mmol, 1.2 eq), and 0.040 g of Pd(PPh3)4 (0.036 mmol, 20 mol %) with 3 mL of toluene, 2 mL of ethanol and 1 mL of 2M aqueous Na2CO3 was heated at 80° C. for 20 h. The reaction was allowed to cool to room temperature, diluted with 25 mL of ethyl acetate and washed with 25 mL of saturated brine. The organic layer was dried over Na2SO4, filtered and concentrated by rotary evaporation to give the crude product which was purified by flash silica gel chromatography eluting with a gradient of 5-50% ethyl acetate in hexane to give 0.042 g of 4-(3′-cyano-biphenyl-4-yl)-4-[5,6-difluoro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester 62 as a pale foam.

Workup

  1. temperatureto cool to room temperature
  2. washwashed with 25 mL of saturated brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customto give the crude product which
  7. customwas purified by flash silica gel chromatography
  8. washeluting with a gradient of 5-50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-55e345f3f73544e9a35091cfc8780b6a
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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