Potassium Carbonate → ethyl 2-(4-((2S,4R)-1-acetyl-4-((isopropoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)acetate

HRID 882249Notes

Reaction equation

HRID 882249 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.[C:14]([N:17]1[C:26]2[C:21](=[CH:22][C:23](B3OC(C)(C)C(C)(C)O3)=[CH:24][CH:25]=2)[C@H:20]([NH:36][C:37](=[O:42])[O:38][CH:39]([CH3:41])[CH3:40])[CH2:19][C@@H:18]1[CH3:43])(=[O:16])[CH3:15].C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>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].O>[C:14]([N:17]1[C:26]2[C:21](=[CH:22][C:23]([C:2]3[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=3)=[CH:24][CH:25]=2)[C@H:20]([NH:36][C:37]([O:38][CH:39]([CH3:41])[CH3:40])=[O:42])[CH2:19][C@@H:18]1[CH3:43])(=[O:16])[CH3:15]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 7020609Ethyl 2-(4-bromophenyl)acetateHCID 681853941-Methylethyl [(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

Product 1

HCID 68185396ethyl 2-(4-((2S,4R)-1-acetyl-4-((isopropoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)acetateYield 59.7%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a flask was charged with ethyl (4-bromophenyl)acetate (0.174 mL, 1.000 mmol), 1-methylethyl [(2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (416 mg, 1 mmol), potassium carbonate (415 mg, 3.00 mmol) and PdCl2(dppf) (73.2 mg, 0.100 mmol) was added 1,4-dioxane (6 mL) and water (2.0 mL) and the flask flushed with nitrogen. The resulting mixture was stirred under microwave irradiation at 120° C. for 30 min then cooled to room temperature. The bulk of dioxane was removed in vacuo and the residue partitioned between EtOAc and water. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography [(25 g column, MeOH/DCM)] to give ethyl 2-(4-((2S,4R)-1-acetyl-4-((isopropoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)acetate (270 mg, 59.7% yield). This compound was used in the next step without further purification. LCMS (HpH, 2 min), Rt=1.16, MH+=453.

Workup

  1. customthe flask flushed with nitrogen
  2. temperaturethen cooled to room temperature
  3. customThe bulk of dioxane was removed in vacuo
  4. customthe residue partitioned between EtOAc and water
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with EtOAc
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by chromatography [(25 g column, MeOH/DCM)]

Sources & evidence

ORD record
ord-08912fad961047a491161db1de2a932e
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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