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

HRID 2354426Notes

Reaction equation

HRID 2354426 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 55.9%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

[(1R)-1-(4-Bromophenyl)-2-(4-morpholinyl)ethyl]methylamine (100 mg, 0.29 mmol) was dissolved in EtOH (5 mL) at room temperature with magnetic stirring. The resulting solution was treated with {4-[(ethyloxy)carbonyl]phenyl}boronic acid (62.9 mg, 0.32 mmol) followed by K2CO3 (122.3 mg, 0.88 mmol) and PdCl2(dppf)2.CH2Cl2 (12.0 mg, 0.015 mmol). The reaction mixture was maintained at 80° C. for 16 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, filtered and then concentrated. The residue was purified by silica gel chromatography (40 g Redisep column, silica, 40 um, 60 Å, 40 mL/min, A: MeOH (with 10% NEt3), B: CH2Cl2, A: 2% for 20 min, 5% for 20 min, detection at 254 nm) to give the title compound as a yellow oil (59.7 mg, 48% yield). MS (ES) m/e 369 [M+H]+.

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. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (40 g Redisep column, silica, 40 um, 60 Å, 40 mL/min
  9. wait5% for 20 min

Sources & evidence

ORD record
ord-6995a5bcb2a64af3a8b7c01d258d830e
Source dataset
uspto-grants-2010_07
Patent number
US07749998B2

Reaction notes

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