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

HRID 2427401Notes

Reaction equation

HRID 2427401 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-33d3b3a15090485a901ec9679733f4ad
Source dataset
uspto-grants-2011_06
Patent number
US07968576B2

Reaction notes

Loading…