N-methyl-2-pyrrolidone → 4'-Fluoro-biphenyl-4-carboxylic acid (6-cyano-1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

HRID 968652Notes

Reaction equation

HRID 968652 reaction equation
C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C([Zn]CC)C.Br[C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[CH2:35][CH:34]([NH:39][C:40]([C:42]1[CH:47]=[CH:46][C:45]([C:48]3[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=3)=[CH:44][CH:43]=1)=[O:41])[CH2:33][CH2:32]2.[CH3:55][N:56]1CCCC1=O>CC([O-])=O.CC([O-])=O.[Pd+2].[C-]#N.[C-]#N.[Zn+2]>[C:55]([C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[CH2:35][CH:34]([NH:39][C:40]([C:42]1[CH:47]=[CH:46][C:45]([C:48]3[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=3)=[CH:44][CH:43]=1)=[O:41])[CH2:33][CH2:32]2)#[N:56]

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidone2×HCID 80271Tri-o-tolylphosphineHCID 590160704'-Fluoro-biphenyl-4-carboxylic acid (6-bromo-1,2,3,4-tetrahydro-naphthalen-2-yl)-amideHCID 178418750HCID 178418750, compound

Product 1

HCID 590160744'-Fluoro-biphenyl-4-carboxylic acid (6-cyano-1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
55 °C

Procedure

A degassed solution of Pd(OAc)2 (0.078 g, 0.35 mmol) and tri-o-tolylphosphine (0.422 g, 1.39 mmol) in N-methylpyrrolidinone (5 mL) is heated at 55° C. for 30 minutes under a nitrogen atmosphere. To this solution is added diethyl zinc(II) (1.0M in hexane, 0.69 mL, 0.69 mmol) and the mixture is maintained at 55° C. for an additional 30 minutes. A premixed solution of 4′-fluoro-biphenyl-4-carboxylic acid (6-bromo-1,2,3,4-tetrahydro-naphthalen-2-yl)-amide, 2, (1.470 g, 3.464 mmol) and Zn(CN)2 (0.405 g, 3.46 mmol) in N-methyl pyrrolidinone (5 mL) is added to the above mixture via cannula. The reaction mixture is then heated at 60° C. overnight. Once cooled, the desired product is then precipitated by adding MeOH to afford 1.43 g (quantitative yield) of an off-white solid. 1H NMR (300 MHz, DMF-D7) δ 8.78 (d, J=7.5 Hz, 1H), 8.28 (d, J=8.7 Hz, 2H), 7.98-8.04 (m, 4H), 7.76-7.81 (m, 2H), 7.55 (d, J=8.7 Hz, 2H), 7.51-7.54 (m, 1H), 4.56 (m, 1H), 3.42-3.50 (m, 1H), 3.16-3.24 (m, 3H), 2.32-2.42 (m, 1H), 2.06-2.20 (m, 1H); 13C NMR (75 MHz, DMF-D7) δ 166.2, 162.6, 142.3, 142.0, 138.1, 134.2, 132.8, 130.7, 129.5, 129.4, 128.4, 126.9, 119.8, 116.3, 116.0, 109.7, 45.9, 30.4, 28.7, 28.0; LRMS: 371.3 (M+H).

Workup

  1. temperatureThe reaction mixture is then heated at 60° C. overnight
  2. temperatureOnce cooled
  3. customthe desired product is then precipitated
  4. additionby adding MeOH

Sources & evidence

ORD record
ord-797d344d76074fb0abbe02e2e201eadd
Source dataset
uspto-grants-2007_12
Patent number
US07304065B2

Reaction notes

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