Potassium Carbonate → HCID 57941526, compound

HRID 1437956Notes

Reaction equation

HRID 1437956 reaction equation
I[C:2]1[CH:3]=[C:4]([N:8]2[C:16](=[O:17])[C:15]3[CH:14]4[C:18]([CH3:20])([CH3:19])[C:11]([CH3:21])([CH2:12][CH2:13]4)[C:10]=3[N:9]2[CH3:22])[CH:5]=[CH:6][CH:7]=1.[C:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O)(=[O:25])[CH3:24].C(=O)([O-])[O-].[K+].[K+]>C(COC)OC.ClCCl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[C:16](=[O:17])[C:15]3[C@@H:14]4[C:18]([CH3:20])([CH3:19])[C@@:11]([CH3:21])([CH2:12][CH2:13]4)[C:10]=3[N:9]2[CH3:22])[CH:3]=1)(=[O:25])[CH3:24]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343092-Acetylphenylboronic acidHCID 69018350HCID 69018350, compound

Product 1

HCID 57941526HCID 57941526, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 2-(3-iodo-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Example 23; 80 mg, 0.2 mmol), 2-acetyl-phenyl-boronic acid (49 mg, 0.29 mmol), potassium carbonate (66 mg, 0.47 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (10 mg, 0.014 mmol) in dimethoxyethane (4 mL) was sealed under argon and heated at 80 degrees overnight and then at 90 degrees over the weekend. The reaction mixture was diluted with dichloromethane, filtered through a cotton plug and frit, evaporated, and purified using an Analogix Intelliflash 280 system (Analogix, Inc., Burlington, Wis.) with an RS-12 column, eluting with 0-80% ethyl acetate/hexanes to give (4S,7R)-2-(2′-acetyl-biphenyl-3-yl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one and unreacted starting material (40 mg, 50%). The product was further purified by preparative HPLC (Gilson 215 collector, Shimadzu prep HPLC system, Leap autoinjector. Solvent (A) 0.05% TFA/H2O (B) 0.035% TFA/ACN, using a linear gradient of 20-80% solvent B in 10 minutes, with a C-18 column, 2.0×10 cm eluting at 20 ml/min and UV-directed collection) followed by lyophilization to give (4S,7R)-2-(2′-acetyl-biphenyl-3-yl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (9 mg, 11%) as a white solid. ES(+)-MS (M+H) 401.

Workup

  1. customwas sealed under argon
  2. temperatureheated at 80 degrees overnight
  3. customat 90 degrees
  4. filtrationfiltered through a cotton plug and frit
  5. customevaporated
  6. custompurified
  7. washeluting with 0-80% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-08ff5f8c234c4a028453d35f34d1c185
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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