Ethanol → HCID 52935236, compound

HRID 2366932Notes

Reaction equation

HRID 2366932 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].C(=O)([O-])[O-].[K+].[K+].Br[C:38]1[S:39][C:40]([CH3:43])=[N:41][N:42]=1.C(O)C>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.C1(C)C=CC=CC=1>[CH3:3][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]([C:38]3[S:39][C:40]([CH3:43])=[N:41][N:42]=3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:1]

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 71719042-Bromo-5-methyl-1,3,4-thiadiazoleHCID 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 52935236HCID 52935236, compoundYield 28.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with 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) (223 mg, 0.536 mmol), potassium carbonate (222 mg, 1.607 mmol), tetrakis(triphenylphosphine)palladium(0) (61.9 mg, 0.054 mmol) and 2-bromo-5-methyl-1,3,4-thiadiazole (125 mg, 0.696 mmol) then filled with ethanol (3 mL) and toluene (3 mL). The resulting mixture was degassed for 15 min under house vacuum (with several quenches with nitrogen) then stirred at 100° C. for 2 h before being cooled to room temperature and left stand still for 16 h. The insoluble material was filtered off and rinsed with AcOEt. Most of the solvent was removed in vacuo and the residue was dissolved in AcOEt. The organic phase was washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 25 G silica cartridge (gradient: 25 to 100% AcOEt in hexanes) gave a material which was then further purified by MDAP (modifier: ammonium bicarbonate) to give 1-methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(5-methyl-1,3,4-thiadiazol-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (60 mg, 0.154 mmol, 28.8% yield) as a white foam.

Workup

  1. customfor a preparation
  2. customThe resulting mixture was degassed for 15 min under house vacuum (with several quenches with nitrogen)
  3. temperaturebefore being cooled to room temperature
  4. waitleft stand still for 16 h
  5. filtrationThe insoluble material was filtered off
  6. washrinsed with AcOEt
  7. customMost of the solvent was removed in vacuo
  8. dissolutionthe residue was dissolved in AcOEt
  9. washThe organic phase was washed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. customPurification of the residue by SP4
  13. customgave a material which
  14. customwas then further purified by MDAP (modifier: ammonium bicarbonate)

Sources & evidence

ORD record
ord-70a62913cefb4bcd805c15aecae6672b
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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