Dichloromethane → Ethyl 4'-[(1R)-1-(methylamino)-2-(4-morpholinyl)ethyl]-4-biphenylcarboxylate

HRID 2114423Notes

Reaction equation

HRID 2114423 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:16][CH3:17])[CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[CH2:18]([O:20][C:21]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)=[O:22])[CH3:19].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CCO.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]>[CH3:17][NH:16][C@H:8]([C:5]1[CH:6]=[CH:7][C:2]([C:26]2[CH:27]=[CH:28][C:23]([C:21]([O:20][CH2:18][CH3:19])=[O:22])=[CH:24][CH:25]=2)=[CH:3][CH:4]=1)[CH2:9][N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343504-Ethoxycarbonylphenylboronic acidHCID 57425542[(1R)-1-(4-bromophenyl)-2-(4-morpholinyl)ethyl]methylamine

Product 1

HCID 57488870Ethyl 4'-[(1R)-1-(methylamino)-2-(4-morpholinyl)ethyl]-4-biphenylcarboxylateYield 107.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolvent

Procedure

[(1R)-1-(4-Bromophenyl)-2-(4-morpholinyl)ethyl]methylamine (20.0 g, 66.9 mmol) was dissolved in EtOH (500 mL) at room temperature with magnetic stirring. The resulting solution was treated with {4-[(ethyloxy)carbonyl]phenyl}boronic acid (14.5 g, 73.6 mmol) followed by K2CO3 (27.7 g, 200.7 mmol) and PdCl2(dppf)2.CH2Cl2 (2.73 g, 3.34 The reaction was maintained at 80° C. overnight. The reaction mixture was cooled to room temperature and then filtered through celite. The filtrate was concentrated and then partitioned between EtOAc and brine. The organic layer was dried over MgSO4, and filtered. The filtrate was concentrated to give the title compound as a brown oil (26.5 g, 80% purity). MS (ES) m/e 369 [M+H]−.

Workup

  1. filtrationfiltered through celite
  2. concentrationThe filtrate was concentrated
  3. custompartitioned between EtOAc and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-bdde097ba0a84f46a41aeeee3312b6d0
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

Loading…