N-methyl-2-pyrrolidone → HCID 71114786, compound

HRID 1624033Notes

Reaction equation

HRID 1624033 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl[C:32]1[CH:37]=[CH:36][C:35]([CH:38]2[CH2:42][C:41](=[O:43])[C:40]([CH3:45])([CH3:44])[CH2:39]2)=[C:34]([F:46])[CH:33]=1.[CH3:47][N:48]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N>[CH3:44][C:40]1([CH3:45])[C:41](=[O:43])[CH2:42][CH:38]([C:35]2[CH:36]=[CH:37][C:32]([C:47]#[N:48])=[CH:33][C:34]=2[F:46])[CH2:39]1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 71114847HCID 71114847, compound

Product 1

HCID 71114786HCID 71114786, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Procedure

Di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (1.75 g, 4.11 mmol) is added to a solution of 4-(4-chloro-2-fluoro-phenyl)-2,2-dimethyl-cyclopentanone (33 g, 137.10 mmol), zinc cyanide (9.66 g, 82.26 mmol), and N-methylpyrrolidone (148.50 mL) at 125° C. and the mixture is stirred for 15 minutes. π-Allylpalladium(II) chloride dimer (0.76 g, 4.11 mmol) is added to the solution and the mixture is stirred for 30 minutes. Diatomaceous earth (15 g) is added and the mixture is cooled to rt. The mixture is filtered through diatomaceous earth and washed with MTBE (450 mL). Water (450 mL) is added and the mixture is extracted with MTBE (150 mL). The mixture is washed with brine, dried over MgSO4, filtered, and concentrated to dryness to give the title compound (34 g, 97%). 1H NMR (300.16 MHz, CDCl3) δ 7.47-7.33 (m, 3H), 3.76-3.63 (m, 1H), 2.83-2.76 (m, 1H), 2.43-2.33 (m, 1H), 2.25 (dd, J=6.3, 12.6 Hz, 1H), 1.91 (t, J=12.3 Hz, 1H), 1.168 (s, 3H), 1.147 (s, 3H).

Workup

  1. stirringthe mixture is stirred for 30 minutes
  2. additionDiatomaceous earth (15 g) is added
  3. filtrationThe mixture is filtered through diatomaceous earth
  4. washwashed with MTBE (450 mL)
  5. additionWater (450 mL) is added
  6. extractionthe mixture is extracted with MTBE (150 mL)
  7. washThe mixture is washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-4d614de358bb46f3b4f259098e8e3ed0
Source dataset
uspto-grants-2014_07
Patent number
US08778984B2

Reaction notes

Loading…