Dichloromethane → tert-butyl 4-(5-cyano-2,3-dihydro-1H-inden-2-yl)piperazine-1-carboxylate

HRID 1519505Notes

Reaction equation

HRID 1519505 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][CH:6]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)[CH2:5]2.ClCCl.[CH3:27][N:28]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[C:27]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][CH:6]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:13][CH2:12]1)[CH2:5]2)#[N:28]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 13387N-methyl-2-pyrrolidoneHCID 86694442tert-Butyl 4-(5-bromo-2,3-dihydro-1H-inden-2-yl)piperazine-1-carboxylate

Product 1

HCID 67517763tert-butyl 4-(5-cyano-2,3-dihydro-1H-inden-2-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 15220664Palladium--triphenylphosphane (1/1)Catalyst

Conditions

Temperature
85 °C

Procedure

To a 5 mL microwave vial was charged with tert-butyl 4-(5-bromo-2,3-dihydro-1H-inden-2-yl)piperazine-1-carboxylate (370 mg, 0.97 mmol), zinc cyanide (114 mg, 0.97 mmol) and palladium triphenylphosphane (1:4) (56 mg, 0.049 mmol). Above mixture was dissolved in N-methyl-2-pyrrolidinone (1 mL). The reaction vial was degassed, filled with N2 and heated in microwave reactor at 85° C. for 2 hr, then at 100° C. for 20 min. To above reaction was added dichloromethane (5 mL), washed with small amount of water. The organic phase was dried over MgSO4, filtered and concentrated. The product was obtained as white solid after purification by flash column chromatography. LC-MS (IE, m/z): 328.3 [M+1]+. 1H NMR (500 MHz, CDCl3, δ in ppm): 7.47 (s, 1H), 7.45 (d, J=8.0 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H), 2.4-3.6 (m, 13H), 1.5 (s, 9H).

Workup

  1. customThe reaction
  2. customvial was degassed
  3. additionfilled with N2
  4. customTo above reaction
  5. washwashed with small amount of water
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe product was obtained as white solid
  10. customafter purification by flash column chromatography

Sources & evidence

ORD record
ord-ee7659b04cc24c219dc4387e7bf12b9e
Source dataset
uspto-grants-2015_07
Patent number
US09073882B2

Reaction notes

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