Potassium Carbonate → 1-[5-Methoxy-2-nitro-4-[3-(1-pyrrolidinyl)propoxy]phenyl]cyclobutanecarbonitrile

HRID 925123Notes

Reaction equation

HRID 925123 reaction equation
[OH:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2([C:14]#[N:15])[CH2:13][CH2:12][CH2:11]2)=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl.Br[CH2:27][CH2:28][CH2:29][N:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>CC#N>[CH3:9][O:8][C:7]1[C:2]([O:1][CH2:27][CH2:28][CH2:29][N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[CH:3][C:4]([N+:16]([O-:18])=[O:17])=[C:5]([C:10]2([C:14]#[N:15])[CH2:11][CH2:12][CH2:13]2)[CH:6]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 13034045HCID 13034045, compoundHCID 921351291-(4-Hydroxy-5-methoxy-2-nitrophenyl)cyclobutanecarbonitrile

Product 1

HCID 1183893681-[5-Methoxy-2-nitro-4-[3-(1-pyrrolidinyl)propoxy]phenyl]cyclobutanecarbonitrileYield 59.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-(4-(hydroxyl)-5-methoxy-2-nitrophenyl)cyclobutanecarbonitrile (0.73 g, 2.93 mmol), from Step 3, in MeCN (20 mL) was added potassium carbonate (1.215 g, 8.79 mmol) and 1-(3-bromopropyl)pyrrolidine hydrochloride (1 g, 4.4 mmol) and stirred at 100° C. for 3 hours. The reaction mixture was concentrated, and extracted with dichloromethane. The combined organic extracts were washed with brine. The organic layer was dried (MgSO4), filtered and concentrated. Purification by flash chromatography (silica gel, 5-20% methanol/dichloromethane) afforded 0.63 g (59%) of 1-(5-methoxy-2-nitro-4-(3-(pyrrolidin-1-yl)propoxy)phenyl)cyclobutanecarbonitrile. 1H NMR (400 MHz, METHANOL-D4) δ 7.65 (s, 1H), 6.94 (s, 1H), 4.14 (t, J=6.1 Hz, 2H), 3.97 (s, 3H), 2.87 (ddd, J=8.6, 5.3, 2.5 Hz, 2H), 2.77-2.67 (m, 2H), 2.68-2.52 (m, 6H), 2.42 (dd, J=14.6, 6.3 Hz, 1H), 2.13-2.01 (m, 2H), 2.01-1.89 (m, 1H), 1.84 (dt, J=6.6, 3.2 Hz, 4H). MS (ESI) m/z 360 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. extractionextracted with dichloromethane
  3. washThe combined organic extracts were washed with brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography (silica gel, 5-20% methanol/dichloromethane)

Sources & evidence

ORD record
ord-af3b0ebb00f34e9a8080b48104507b3a
Source dataset
uspto-grants-2016_03
Patent number
US09284272B2

Reaction notes

Loading…