Sodium Carbonate → cis-2,6-Dimethyl-piperazine-1-carboxylic acid 2,4-difluoro-2'-methoxy-biphenyl-3-ylmethyl ester

HRID 1794135Notes

Reaction equation

HRID 1794135 reaction equation
C(OC([N:8]1[CH2:13][C@@H:12]([CH3:14])[N:11]([C:15]([O:17][CH2:18][C:19]2[C:24]([F:25])=[CH:23][CH:22]=[C:21](Br)[C:20]=2[F:27])=[O:16])[C@@H:10]([CH3:28])[CH2:9]1)=O)(C)(C)C.[CH3:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.Cl[Pd]Cl.[Fe+2]>[F:27][C:20]1[C:19]([CH2:18][O:17][C:15]([N:11]2[C@H:12]([CH3:14])[CH2:13][NH:8][CH2:9][C@@H:10]2[CH3:28])=[O:16])=[C:24]([F:25])[CH:23]=[CH:22][C:21]=1[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[O:30][CH3:29]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 69141723cis-2,6-Dimethyl-piperazine-1,4-dicarboxylic acid 1-(3-bromo-2,6-difluoro-benzyl) ester 4-tert-butyl ester

Product 1

HCID 69142364cis-2,6-Dimethyl-piperazine-1-carboxylic acid 2,4-difluoro-2'-methoxy-biphenyl-3-ylmethyl ester

Reagents, catalysts & solvents 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 46.33 mg (0.1 mmol) cis-2,6-dimethyl-piperazine-1,4-dicarboxylic acid 1-(3-bromo-2,6-difluoro-benzyl) ester 4-tert-butyl ester, 16.71 mg (0.11 mmol) 2-methoxyphenylboronic acid, 3.65 mg (0.005 mmol) dichloro(1,1′-bis(diphenylphosphino) ferrocene)palladium (II) dichloromethane adduct and 0.11 ml of a 2M Na2CO3 aq. solution in 1.2 ml dioxane was heated for 17 h to 85° C. The mixture was filtered and 0.15 ml 4N HCl in dioxane was added and the mixture heated for 3 h to 65° C. After cooling to ambient temperature 0.2 ml triethylamine and water were added to dissolve the mixture. The solution was subjected to reversed phase preparative HPLC eluting with a water/acetonitrile gradient to yield after evaporation of the solvents 28.2 mg (66%) of the title compound. MS (ISP): 391 MH+

Workup

  1. temperaturewas heated for 17 h to 85° C
  2. filtrationThe mixture was filtered
  3. addition0.15 ml 4N HCl in dioxane was added
  4. temperaturethe mixture heated for 3 h to 65° C
  5. additionwere added
  6. dissolutionto dissolve the mixture
  7. washeluting with a water/acetonitrile gradient
  8. customto yield
  9. customafter evaporation of the solvents 28.2 mg (66%) of the title compound

Sources & evidence

ORD record
ord-c0c308b23c0143edb99856873973bbb4
Source dataset
uspto-grants-2006_04
Patent number
US07022707B2

Reaction notes

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