Toluene → HCID 67218888, compound

HRID 1788281Notes

Reaction equation

HRID 1788281 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)([CH:14]([O:23][C:24]2[NH:28][C:27]3[CH:29]=[C:30]([Cl:34])[C:31]([Cl:33])=[CH:32][C:26]=3[N:25]=2)[CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[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)([CH:14]([O:23][C:24]2[NH:28][C:27]3[CH:29]=[C:30]([Cl:34])[C:31]([Cl:33])=[CH:32][C:26]=3[N:25]=2)[CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 67219407HCID 67219407, compound

Product 1

HCID 67218888HCID 67218888, compoundYield 79.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 0.105 g of 4-(4-bromo-phenyl)-4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-piperidine-1-carboxylic acid tert-butyl ester 51 (0.144 mmol, 1 eq), 0.024 g of 3-cyanophenyl boronic acid (0.16 mmol, 1.1 eq), and 0.034 g of Pd(PPh3)4 (0.03 mmol, 20 mol %) was mixed with 3 mL of toluene, 2 mL of ethanol and 1 mL of 2M aqueous Na2CO3 and then heated at 80° C. for 20 h while stirring. 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 extracts were dried over Na2SO4, filtered and concentrated by rotary evaporation to give the crude product which was purified by flash column chromatography eluting with a gradient of 5-20% ethyl acetate in hexane to give 0.081 g of 4-(3′-cyano-biphenyl-4-yl)-4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-piperidine-1-carboxylic acid tert-butyl ester 52 as a pale foam: 1H NMR (300 MHz, CDCl3): δ 7.82-7.76 (m, 2H), 7.59-7.48 (m, 7H), 7.13-7.10 (m, 1H), 5.17 (s, 2H), 4.53 (s, 2H), 3.85-3.80 (br. d, 2H), 3.41-3.36 (t, 2H), 3.18-3.10 (t, 2H), 2.36-2.3 (d, 2H), 2.00-1.96 (t, 2H), 1.44 (s, 9H), 0.83-0.77 (t, 2H), 0.10 (s, 9H).

Workup

  1. temperatureto cool to room temperature
  2. washwashed with 25 mL of saturated brine
  3. dry with materialThe organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customto give the crude product which
  7. customwas purified by flash column chromatography
  8. washeluting with a gradient of 5-20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-e63f3163b5de49a88ff24da4241e7ea5
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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