Diethyl Ether → HCID 86722464, compound

HRID 718850Notes

Reaction equation

HRID 718850 reaction equation
CC([O-])(C)C.[K+].CCO[CH2:10][CH3:11].[F:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:23]3=[N:24][C:25]4[CH2:26][CH2:27][CH2:28]C(=O)[C:30]=4[CH:31]=[C:22]3[CH:21]=[N:20]2)=[CH:15][CH:14]=1.O1CCOCC1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCCCCCC.CCOC(C)=O>[F:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]2[C:23]3=[N:24][C:25]4[CH2:26][CH2:27][CH2:28][C:10](=[CH2:11])[C:30]=4[CH:31]=[C:22]3[CH:21]=[N:20]2)=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 312751,4-DioxaneHCID 23665647Potassium tert-butoxideHCID 86722463HCID 86722463, compound

Product 1

HCID 86722464HCID 86722464, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 21899848Ethylacetate heptaneSolvent2×

Procedure

A flask was charged with potassium 2-methylpropan-2-olate (45.4 g, 404 mmol), Et2O (1000 mL) and methyltriphenylphosphonium bromide (141 g, 395 mmol). The mixture was stirred for about 2 h at rt then 1-(4-fluorophenyl)-7,8-dihydro-1H-pyrazolo[3,4-b]quinolin-5(6H)-one (112, R1=4-Fluorophenyl) (55.5 g, 197 mmol) was added over about 15 min. The mixture was stirred at rt for about 15 h. 1,4-Dioxane (100 mL) was added to the reaction mixture and stirring was continued for about 4 h. Solids were removed by filtration and the pad was washed with 600 mL Et2O. The filtrate was concentrated under reduced pressure then EtOAc (250 mL) and heptane (750 mL) was added. The solids were removed by filtration then the pad was washed with 3 portions of 3:1 heptane/EtOAc (100 mL). The filtrate was concentrated under reduced pressure to yield a slurry. A mixture of 3:1 heptane/EtOAc (100 mL) was added to the material then the slurry was poured onto a pad of 600 grams of silica pre-gelled with 3:1 Heptane/EtOAc. The pad was washed with 3:1 Heptane/EtOAc (6 L) until TLC (3:1 Heptane/EtOAc, visualized by UV) showed essentially no more desired product in the filtrate. The filtrate was concentrated under reduced pressure to yield 1-(4-fluorophenyl)-5-methylene-5,6,7,8-tetrahydro-1H-pyrazolo[3,4-b]quinoline (113, R1=4-Fluorophenyl) (44.0 g, 80%): LC/MS, method 3, Rt=2.87 min, MS m/z 280 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.63 (s, 1H), 8.37 (s, 1H), 8.34-8.27 (m, 2H), 7.45-7.38 (m, 2H), 5.67 (d, J=0.8 Hz, 1H), 5.09 (d, J=0.9 Hz, 1H), 3.10 (t, J=6.4 Hz, 2H), 2.63-2.56 (m, 2H), 1.97-1.87 (m, 2H).

Workup

  1. stirringThe mixture was stirred at rt for about 15 h
  2. stirringstirring
  3. waitwas continued for about 4 h
  4. customSolids were removed by filtration
  5. washthe pad was washed with 600 mL Et2O
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. additionEtOAc (250 mL) and heptane (750 mL) was added
  8. customThe solids were removed by filtration
  9. washthe pad was washed with 3 portions of 3:1 heptane/EtOAc (100 mL)
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customto yield a slurry
  12. additionwas added to the material
  13. washThe pad was washed with 3:1 Heptane/EtOAc (6 L) until TLC (3:1 Heptane/EtOAc, visualized by UV)
  14. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-eb25bf84b23046a693e2fd88f15d369e
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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