Binap, (A+-)- → HCID 67337338, compound

HRID 1670542Notes

Reaction equation

HRID 1670542 reaction equation
[NH2:1][CH2:2][C:3]1[C:13]2[CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9][CH2:8][C:7]=2[CH:6]=[CH:5][C:4]=1[Cl:21].Br[C:23]1[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:28])=[CH:25][CH:24]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>O.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:17]([O:16][C:14]([N:10]1[CH2:11][CH2:12][C:13]2[C:3]([CH2:2][NH:1][C:23]3[CH:24]=[CH:25][C:26]([C:27](=[O:28])[NH:29][CH:30]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)=[CH:37][CH:38]=3)=[C:4]([Cl:21])[CH:5]=[CH:6][C:7]=2[CH2:8][CH2:9]1)=[O:15])([CH3:18])([CH3:20])[CH3:19]

Participants

9

Reactant 4

HCID 634876Binap, (A+-)-HCID 2843132HCID 2843132, compoundHCID 23676156Sodium t-butoxideHCID 59822294HCID 59822294, compound

Product 1

HCID 67337338HCID 67337338, compoundYield 54.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

Under a nitrogen atmosphere, add 6-aminomethyl-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (500 mg, 1.6 mmol), 4-bromo-N-cycloheptyl-benzamide (520 mg, 1.8 mmol), palladium(II) acetate (35 mg, 0.16 mmol), BINAP (150 mg, 0.24 mmol) and sodium-t-butoxide (460 mg, 4.8 mmol) to toluene (10 mL). Heat the mixture at 70° C. for 1 h. Cool the mixture to room temperature and dilute with water and DCM. Separate the layers and extract the aqueous phase with DCM. Wash the combined organic extracts with water and brine. Dry the organic layer over Na2SO4, filter and concentrate in vacuo. Purify the residue by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 17:1 gradient) to obtain 3-tert-butoxycarbonyl-7-chloro-6-[(4-cycloheptylcarbamoyl-phenylamino)-methyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (460 mg, 54%). MS (APCI+) m/z: 526 (M+H)+.

Workup

  1. temperatureCool the mixture to room temperature
  2. customSeparate the layers
  3. extractionextract the aqueous phase with DCM
  4. washWash the combined organic extracts with water and brine
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify the residue by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 17:1 gradient)

Sources & evidence

ORD record
ord-8c7028a943064beb8ab8ab77b71d848e
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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