Binap, (A+-)- → HCID 44221920, compound

HRID 1947380Notes

Reaction equation

HRID 1947380 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:18][C@@H:17]2[C@@H:13]([NH:14][CH2:15][CH2:16]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][C:30](OS(C(F)(F)F)(=O)=O)=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)#[N:20].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:18][C@@H:17]2[C@@H:13]([N:14]([C:30]3[CH:29]=[CH:28][C:27]([C:24]4[CH:23]=[CH:22][C:21]([C:19]#[N:20])=[CH:26][CH:25]=4)=[CH:32][CH:31]=3)[CH2:15][CH2:16]2)[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 44221501(3aR,6aR)-Hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid benzyl esterHCID 44221918Trifluoro-methanesulfonic acid 4'-cyano-biphenyl-4-yl ester

Product 1

HCID 44221920HCID 44221920, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

The product of Example 1B (trifluoro-methanesulfonic acid 4′-cyano-biphenyl-4-yl ester) (135 mg, 0.55 mmole), the product of Example 1C (198 mg, 0.61 mmole), palladium acetate (2.7 mg, 0.012 mmole), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP, 20 mg, 0.033 mmole) and sodium tert-butoxide (80 mg, 0.83 mmole) were mixed in 1.5 ml of toluene and heated at 80° C. under N2 for 16 hours. The mixture was cooled to room temperature, diluted with water and extracted with dichloromethane (3×). The combined organics were dried over sodium sulfate and concentrated to provide the crude product, which was purified by chromatography (5% methanol in dichloromethane) to provide the title compound. MS: (M+H)+=424.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with dichloromethane (3×)
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. concentrationconcentrated
  5. customto provide the crude product, which
  6. customwas purified by chromatography (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-f05a91b01c254b72987198cf225c6c13
Source dataset
uspto-grants-2013_03
Patent number
US08399468B2

Reaction notes

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