Sodium hydride → trans-[2-(4-Fluorophenyl)cyclopropyl]-(4-isopropylpiperazin-1-yl)methanone

HRID 561068Notes

Reaction equation

HRID 561068 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7](/[CH:10]=[CH:11]/[C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH:20]([CH3:22])[CH3:21])[CH2:16][CH2:15]2)=[O:13])=[CH:6][CH:5]=1.CO.[CH2:25](Cl)Cl>CS(C)=O>[F:3][C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]2[CH2:25][C@H:11]2[C:12]([N:14]2[CH2:15][CH2:16][N:17]([CH:20]([CH3:22])[CH3:21])[CH2:18][CH2:19]2)=[O:13])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21226129Dichloromethane methanolHCID 57618979(E)-3-(4-Fluorophenyl)-1-(4-isopropylpiperazin-1-yl)prop-2-en-1-one

Product 1

HCID 25196566trans-[2-(4-Fluorophenyl)cyclopropyl]-(4-isopropylpiperazin-1-yl)methanoneYield 57%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a vigorously stirring mixture of NaH (300 mg, 12.5 mmol) in DMSO (30 mL) at ambient temperature under an argon (g) atmosphere was added (CH3)3S(I)O (2.50 g, 11.4 mmol) in small portions over 1 min. Following complete addition, the reaction was stirred for 50 min before the rapid dropwise addition of DMSO (10 mL) solution of 10A (1.57 g, 5.68 mmol). After ca. 50 h the reaction was quenched with H2O (80 mL) and extracted into EtOAc (75 mL). The phases were separated and the aq. phase was further extracted with EtOAc (2×70 mL). The combined organics were washed with H2O (15 mL), brine (15 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting gum was subjected to flash chromatography (SiO2—40 g; gradient elution: 1% MeOH/DCM for 3 min then 1%-5% MeOH/DCM over 20 min at 40 mL/min) to afford 947 mg 10B (57% yield). m/z (ES+) M+1=291.3; HPLC tR=1.52 min. 1H NMR (500 MHz, CDCl3) δ 7.07 (dd, J=8.7, 5.3 Hz, 2H), 6.96 (t, J=8.7 Hz, 2H), 3.63 (dd, J=14.5, 5.0 Hz, 4H), 2.71 (ddd, J=13.0, 6.7, 6.6 Hz, 1H), 2.57-2.44 (m, 4H), 1.90 (ddd, J=8.3, 5.4, 4.3 Hz, 1H), 1.68-1.56 (m, 2H), 1.21 (ddd, J=8.4, 6.3, 4.3 Hz, 1H), 1.04 (d, J=6.4 Hz, 6H).

Workup

  1. additionaddition
  2. customAfter ca. 50 h the reaction was quenched with H2O (80 mL)
  3. extractionextracted into EtOAc (75 mL)
  4. customThe phases were separated
  5. extractionthe aq. phase was further extracted with EtOAc (2×70 mL)
  6. washThe combined organics were washed with H2O (15 mL), brine (15 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. washgradient elution

Sources & evidence

ORD record
ord-d12a62f94aca4021829361298405e9d7
Source dataset
uspto-grants-2011_11
Patent number
US08063215B2

Reaction notes

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