Ethanol → HCID 52934794, compound

HRID 2366960Notes

Reaction equation

HRID 2366960 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(=O)C)[C@@H:9]([CH3:29])[CH2:8]1)[CH3:3].Cl[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:44]([OH:46])[CH3:45]>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:44]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=3)=[CH:13][CH:12]=2)[C@H:7]([NH:6][C:5](=[O:30])[O:4][CH:2]([CH3:1])[CH3:3])[CH2:8][C@@H:9]1[CH3:29])(=[O:46])[CH3:45]

Participants

7

Reactant 4

HCID 702EthanolHCID 79772-ChloropyridineHCID 11430Potassium CarbonateHCID 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 52934794HCID 52934794, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 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) (108 mg, 0.259 mmol), 2-chloropyridine (35.3 mg, 0.311 mmol), potassium carbonate (108 mg, 0.778 mmol) and tetrakis(triphenylphosphine)palladium(0) (14.99 mg, 0.013 mmol) in ethanol (2.5 mL) and toluene (2.5 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 (30 mL) and water (15 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 MDAP (reversed phase, water/acetonitrile, modifier: ammonium bicarbonate) gave 1-methylethyl [(2S,4R)-1-acetyl-2-methyl-6-(2-pyridinyl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (32.1 mg, 0.087 mmol, 34%) 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 (30 mL) and water (15 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 MDAP (reversed phase, water/acetonitrile, modifier: ammonium bicarbonate)

Sources & evidence

ORD record
ord-9f13c62cd7a342eab27ee458cbc03ac0
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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