Potassium Hydroxide → 5-Fluoro-8-(4-(4-(6-methoxyquinolin-8-yl)piperazin-1-yl)piperidin-1-yl)Quinoline

HRID 2242009Notes

Reaction equation

HRID 2242009 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:15][O:16][C:17]1[CH:18]=[C:19]2[C:24](=[C:25]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[CH:26]=1)[N:23]=[CH:22][CH:21]=[CH:20]2.[F:33][C:34]1[CH:43]=[CH:42][C:41]([N:44]2[CH2:49][CH2:48][C:47](=O)[CH2:46][CH2:45]2)=[C:40]2[C:35]=1[CH:36]=[CH:37][CH:38]=[N:39]2.[OH-].[K+]>C1(C)C=CC=CC=1>[F:33][C:34]1[CH:43]=[CH:42][C:41]([N:44]2[CH2:49][CH2:48][CH:47]([N:30]3[CH2:29][CH2:28][N:27]([C:25]4[CH:26]=[C:17]([O:16][CH3:15])[CH:18]=[C:19]5[C:24]=4[N:23]=[CH:22][CH:21]=[CH:20]5)[CH2:32][CH2:31]3)[CH2:46][CH2:45]2)=[C:40]2[C:35]=1[CH:36]=[CH:37][CH:38]=[N:39]2

Participants

6

Reactant 4

HCID 14797Potassium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 184141776-Methoxy-8-(piperazin-1-YL)quinolineHCID 592048481-(5-Fluoroquinolin-8-yl)piperidin-4-one

Product 1

HCID 120041425-Fluoro-8-(4-(4-(6-methoxyquinolin-8-yl)piperazin-1-yl)piperidin-1-yl)Quinoline

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
30 °C

Procedure

Toluene (118 g), sodium triacetoxyborohydride (44.5 g) were mixed at 0° C. to room temperature. To this mixture was charged a premixed toluene solution of 6-methoxy-8-(1-piperazinyl)quinoline (Step 1, 160 g, 27.4 wt % in toluene) and 1-(5-fluoroquinolin-8-yl)piperidin-4-one (Step 3, 41 g). The resulting mixture was stirred for 2 to 3 hours at about 30° C. KOH solution (443 g 9% in water) was charged to quench the residual sodium triacetoxyborohydride. Heptane (118 g) was added to further precipitate the product. The product was then filtered and washed with ethanol (2×100 ml). Yield 68 g, 86%. This crude product (67 g) was dissolved in 586 g dichloromethane and passed through a charcoal/celite pad to remove palladium. The dichloromethane was distilled off while 400 g of ethanol was slowly added at the same time. The resulting slurry was filtered and washed with ethanol twice (65 g+100 g). The product was dried in oven at 55° C. overnight. Purification recovery yield 59.9 g, 89.4%.

Workup

  1. customto quench the residual sodium triacetoxyborohydride
  2. additionHeptane (118 g) was added to further precipitate the product
  3. filtrationThe product was then filtered
  4. washwashed with ethanol (2×100 ml)
  5. dissolutionThis crude product (67 g) was dissolved in 586 g dichloromethane
  6. customto remove palladium
  7. distillationThe dichloromethane was distilled off while 400 g of ethanol
  8. additionwas slowly added at the same time
  9. filtrationThe resulting slurry was filtered
  10. washwashed with ethanol twice (65 g+100 g)
  11. customThe product was dried in oven at 55° C. overnight
  12. customPurification recovery yield 59.9 g, 89.4%

Sources & evidence

ORD record
ord-91983d78c4d7472da52f18950538c93b
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Reaction notes

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