Potassium Phosphate, Tribasic → (2R,6R,11S)-6,11-Dimethyl-8-(2-methyl-pyrimidin-4-yl)-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine

HRID 536665Notes

Reaction equation

HRID 536665 reaction equation
C(OC([N:8]1[CH2:15][CH2:14][C@:13]2([CH3:18])[C@H:16]([CH3:17])[C@H:9]1[CH2:10][C:11]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][C:12]=12)=O)(C)(C)C.Cl[C:27]1[CH:32]=[CH:31][N:30]=[C:29]([CH3:33])[N:28]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C(O)CCC.CC([O-])=O.CC([O-])=O.[Pd+2].C(OCC)(=O)C>[CH3:18][C@:13]12[C@H:16]([CH3:17])[C@H:9]([NH:8][CH2:15][CH2:14]1)[CH2:10][C:11]1[CH:22]=[CH:21][C:20]([C:27]3[CH:32]=[CH:31][N:30]=[C:29]([CH3:33])[N:28]=3)=[CH:19][C:12]2=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 4244474-Chloro-2-methylpyrimidineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 58123740(2R,6R,11S)-6,11-Dimethyl-8-borono-1,2,5,6-tetrahydro-4H-2,6-methano-benzo[d]azocine-3-carboxylic acid tert-butyl ester

Product 1

HCID 58123804(2R,6R,11S)-6,11-Dimethyl-8-(2-methyl-pyrimidin-4-yl)-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Pd(OAc)2 (3.3 mg) is added to a mixture of (2R,6R,11S)-6,11-dimethyl-8-borono-1,2,5,6-tetrahydro-4H-2,6-methano-benzo[d]azocine-3-carboxylic acid tert-butyl ester (0.30 g), 4-chloro-2-methyl-pyrimidine (93 mg), K3PO4 (0.31 g), and 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (11.5 mg) in n-butanol (2 mL) under argon atmosphere. The resulting mixture is heated to 100° C. and stirred at this temperature overnight. After cooling to room temperature, ethyl acetate is added, the resulting mixture is filtered, and the filtrate is concentrated under reduced pressure. The residue is taken up in CH2Cl2 (3 mL) and treated with F3CCO2H (0.5 mL) for 1 h. Then, the solution is concentrated and the residue is purified by HPLC on reversed phase (MeCN/H2O/NH3) to afford the title compound.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe resulting mixture is filtered
  3. concentrationthe filtrate is concentrated under reduced pressure
  4. additiontreated with F3CCO2H (0.5 mL) for 1 h
  5. concentrationThen, the solution is concentrated
  6. customthe residue is purified by HPLC on reversed phase (MeCN/H2O/NH3)

Sources & evidence

ORD record
ord-1a9fc226ad4841b3a271cf4109c03c67
Source dataset
uspto-grants-2014_10
Patent number
US08859580B2

Reaction notes

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