Aniline → (2-Oxo-1-(3-phenylamino-benzyl)-azepan-3-yl]-carbamic acid tert-butyl ester

HRID 30306Notes

Reaction equation

HRID 30306 reaction equation
[C:1]([O:5][C:6](=[O:24])[NH:7][CH:8]1[CH2:14][CH2:13][CH2:12][CH2:11][N:10]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18](I)[CH:17]=2)[C:9]1=[O:23])([CH3:4])([CH3:3])[CH3:2].[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CC(C)([O-])C.[Na+]>C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1.O.CC(O)=O.CC(O)=O.[Pd]>[C:1]([O:5][C:6](=[O:24])[NH:7][CH:8]1[CH2:14][CH2:13][CH2:12][CH2:11][N:10]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([NH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:17]=2)[C:9]1=[O:23])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 6115AnilineHCID 23555228[1-(3-Iodo-benzyl)-2-oxo-azepan-3-yl]-carbamic acid tert-butyl esterHCID 23676156Sodium t-butoxide

Product 1

HCID 68950358(2-Oxo-1-(3-phenylamino-benzyl)-azepan-3-yl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 4144353Palladium (II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 634876Binap, (A+-)-Solvent2×

Conditions

Temperature
80 °C

Procedure

In a 100 ml round bottomed flask Binap, (S)-(−)2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl, (0.210 g, 0.3375 mmol) dissolved in 15 mL toluene was stirred at 80° C. for 1 minute. To the flask cooled to room temperature under inert atmosphere Pd(OAC)2 (0.050 g, 0.225 mmol) was added and the solution was stirred at room temperature for 2 minutes. To the reaction mixture [1-(3-Iodo-benzyl)-2-oxo-azepan-3-yl]-carbamic acid tert-butyl ester (1.0 g, 2.25 mmol) dissolved in 15 mL toluene, aniline (1.047 g, 11.25 mmol) and Sodium tert-butoxide (0.259 g, 2.70 mmol) were added and the solution was stirred at 80° C. for 18 h. The reaction was cooled to room temperature, diluted with 200 mL of water, and extracted twice with 100 mL of ethyl acetate. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated to an oil. The oil was purified on flash silica gel column using 10-30% ethyl acetate in hexanes as eluent to yield 0.562 g (61%). MS (ESI) M+H=432.5

Workup

  1. additionwas added
  2. stirringthe solution was stirred at room temperature for 2 minutes
  3. stirringthe solution was stirred at 80° C. for 18 h
  4. temperatureThe reaction was cooled to room temperature
  5. extractionextracted twice with 100 mL of ethyl acetate
  6. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to an oil
  9. customThe oil was purified on flash silica gel column
  10. customto yield 0.562 g (61%)

Sources & evidence

ORD record
ord-cd1d4117fe8b431f866b08b35adbdc96
Source dataset
uspto-grants-2008_09
Patent number
US07423033B2

Reaction notes

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