Potassium Carbonate → HCID 67196970, compound

HRID 2366889Notes

Reaction equation

HRID 2366889 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:3].Br[C:32]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][C:40]([O:42][CH2:43][C:44]2C=CC=CC=2)=[O:41])=[CH:34][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:26]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:32]3[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:34][CH:33]=3)=[CH:13][CH:12]=2)[C@H:7]([NH:6][C:5]([O:4][CH:2]([CH3:3])[CH3:1])=[O:30])[CH2:8][C@@H:9]1[CH3:29])(=[O:28])[CH3:27]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 67198131HCID 67198131, compoundHCID 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 67196970HCID 67196970, compoundYield 35%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 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 (for a preparation see Intermediate 52) (100 mg, 0.240 mmol), phenylmethyl 3-(4-bromophenyl)propanoate (92 mg, 0.288 mmol), potassium carbonate (100 mg, 0.721 mmol) and tetrakis(triphenylphosphine)palladium(0) (13.88 mg, 0.012 mmol) in ethanol (2.5 mL) and toluene (2.500 mL) was degassed for 15 min under house vacuum and quenched several times with nitrogen, and then was heated at 100° C. for 1 h before being cooled to room temperature and partitioned between AcOEt (35 mL) and water (20 mL). The layers were separated and the aqueous phase was extracted with AcOEt (15 mL). The combined organic phases were washed with brine (15 mL), dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 40 to 70% AcOEt in Hexanes) gave a residue which was further purified by MDAP (modifier: formic acid) to give ethyl 3-{4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]phenyl}propanoate (39.7 mg, 0.085 mmol, 35%) as a white solid.

Workup

  1. customwas degassed for 15 min under house vacuum
  2. customquenched several times with nitrogen
  3. temperaturebefore being cooled to room temperature
  4. custompartitioned between AcOEt (35 mL) and water (20 mL)
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with AcOEt (15 mL)
  7. washThe combined organic phases were washed with brine (15 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customPurification of the residue by flash chromatography on silica gel (gradient: 40 to 70% AcOEt in Hexanes)
  11. customgave a residue which
  12. customwas further purified by MDAP (modifier: formic acid)

Sources & evidence

ORD record
ord-8773ec59dbc54664bb9df8a8b7a01366
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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