Dichloromethane → (1R)-N-Methyl-1-[3'-(methyloxy)-4-biphenylyl]-2-(4-morpholinyl)ethanamine

HRID 2114418Notes

Reaction equation

HRID 2114418 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.[O:18]([C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1)[CH3:19].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>O1CCOCC1.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]>[CH3:17][NH:16][C@H:8]([C:5]1[CH:6]=[CH:7][C:2]([C:24]2[CH:23]=[CH:22][CH:21]=[C:20]([O:18][CH3:19])[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 2734370(3-Methoxyphenyl)boronic acidHCID 57425542[(1R)-1-(4-bromophenyl)-2-(4-morpholinyl)ethyl]methylamine

Product 1

HCID 57488867(1R)-N-Methyl-1-[3'-(methyloxy)-4-biphenylyl]-2-(4-morpholinyl)ethanamineYield 86.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

[(1R)-1-(4-Bromophenyl)-2-(4-morpholinyl)ethyl]methylamine (3.5 g, 11.7 mmol) was dissolved in a dioxane/H2O solution (140 mL, 5:2 volume ratio) at room temperature with magnetic stirring. The resulting solution was treated with 3-methoxylbenzene boronic acid (1.76 g, 12.9 mmol) followed by K2CO3 (4.85 g, 3.51 mmol) and PdCl2(dppf)2.CH2Cl2 (0.48 g, 0.59 mmol). The reaction was maintained at 100° C. for 5 h. 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, and the residue was purified by silica gel chromatography (120 g Redisep column, silica, 40 um, 60 Å, 80 mL/min, A: MeOH (with 10% NEt3), B: CH2Cl2, A: 2% for 20 min, 5% for 20 min, 10% for 10 min; detection at 254 nm) to give the title compound as a yellow oil (3.3 g, 85%). MS (ES) m/e 327 [M+H]1 .

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through celite
  3. concentrationThe filtrate was concentrated
  4. custompartitioned between EtOAc and brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customthe residue was purified by silica gel chromatography (120 g Redisep column, silica, 40 um, 60 Å, 80 mL/min
  9. wait5% for 20 min
  10. wait10% for 10 min

Sources & evidence

ORD record
ord-cd33153abf0f4fdea8c0dd63cdd009dc
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

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