Dichloromethane → trans-2-(Trimethylsilyl)ethyl-2-({4'-[(5-methyl-1,3-benzoxazol-2-yl)amino]biphenyl-4-yl}carbonyl)cyclohexanecarboxylate

HRID 30937Notes

Reaction equation

HRID 30937 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[O:10][C:11]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:12]=3[N:13]=2)=[CH:4][CH:3]=1.[CH3:19][Si:20]([CH3:42])([CH3:41])[CH2:21][CH2:22][O:23][C:24]([C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[C:32](=[O:40])[C:33]1[CH:38]=[CH:37][C:36](Br)=[CH:35][CH:34]=1)=[O:25].C([O-])(O)=O.[Na+].ClCCl>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCO.C1(C)C=CC=CC=1>[CH3:19][Si:20]([CH3:42])([CH3:41])[CH2:21][CH2:22][O:23][C:24]([C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[C:32]([C:33]1[CH:34]=[CH:35][C:36]([C:2]2[CH:7]=[CH:6][C:5]([NH:8][C:9]3[O:10][C:11]4[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:12]=4[N:13]=3)=[CH:4][CH:3]=2)=[CH:37][CH:38]=1)=[O:40])=[O:25]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 21985825N-(4-Bromophenyl)-5-methyl-1,3-benzoxazol-2-amineHCID 58681290trans-(Trimethylsilyl)ethyl 2-(4-bromobenzoyl)cyclohexanecarboxylate

Product 1

HCID 58681282trans-2-(Trimethylsilyl)ethyl-2-({4'-[(5-methyl-1,3-benzoxazol-2-yl)amino]biphenyl-4-yl}carbonyl)cyclohexanecarboxylateYield 50.2%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

N-(4-Bromophenyl)-5-methyl-1,3-benzoxazol-2-amine (76.70 mg, 0.25 mmol) and trans-2-(trimethylsilyl)ethyl-2-(4-bromobenzoyl)cyclohexanecarboxylate (105.45 mg, 0.23 mmol) were combined in a clean dry flask under argon. Toluene (25 mL), EtOH (8 mL), and saturated aqueous NaHCO3 (5 mL) were added, and the resulting solution was degassed by bubbling with argon for 30 minutes. Then, [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II), 1:1 complex with dichloromethane (18.78 mg, 0.02 mmol) was added, and the resulting mixture was heated at 90° C. for 16 h. The reaction mixture was then diluted with EtOAc and passed through a Celite® pad, and the solvent was removed by rotary evaporation. Silica gel chromatography (Biotage cartridge), eluting with 25% EtOAc in hexane gave trans-2-(trimethylsilyl)ethyl-2-({4′-[(5-methyl-1,3-benzoxazol-2-yl)amino]biphenyl-4-yl}carbonyl)cyclohexanecarboxylate (64 mg, 50%). 1H NMR (400 MHz, CD2Cl2) δ−0.013 (s, 9H), 0.88 (m, 2H), 1.41 (m, 3H), 1.71˜2.15 (m, 5H), 2.44 (s, 3H), 2.73 (m, 1H), 3.88 (m, 1H), 4.08 (m, 2H), 7.08 (d, 1H), 7.21 (s, 1H), 7.33 (d, 1H), 7.67 (m, 2H), 7.69 (m, 2H), 7.73 (m, 2H), 7.89 (m, 1H), 7.91 (m, 1H).

Workup

  1. customthe resulting solution was degassed
  2. customby bubbling with argon for 30 minutes
  3. customthe solvent was removed by rotary evaporation
  4. washSilica gel chromatography (Biotage cartridge), eluting with 25% EtOAc in hexane

Sources & evidence

ORD record
ord-4bd9de63d624422091e51dd7619d8ae5
Source dataset
uspto-grants-2008_09
Patent number
US07423156B2

Reaction notes

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