4-Methoxybenzylamine → HCID 66717175, compound

HRID 1028679Notes

Reaction equation

HRID 1028679 reaction equation
[F:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([C:11]2[C:12]([CH:21]=O)=[CH:13][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=2)=[C:4]([O:23][CH3:24])[CH:3]=1.[Si]([C:29]#[N:30])(C)(C)C.[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH2:38])=[CH:35][CH:34]=1>C(Cl)Cl.CO.[Zn+2].[I-].[I-]>[F:1][C:2]1[C:7]([CH:8]([CH3:9])[CH3:10])=[CH:6][C:5]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][C:12]=2[CH:21]([NH:38][CH2:37][C:36]2[CH:39]=[CH:40][C:33]([O:32][CH3:31])=[CH:34][CH:35]=2)[C:29]#[N:30])=[C:4]([O:23][CH3:24])[CH:3]=1

Participants

7

Reactant 3

HCID 754524-MethoxybenzylamineHCID 82115Trimethylsilyl cyanideHCID 591352254′-Fluoro-2′-methoxy-5′-(1-methylethyl)-4-(trifluoromethyl)[1,1′-biphenyl]-2-carboxaldehyde2×

Product 1

HCID 66717175HCID 66717175, compound

Reagents, catalysts & solvents 3

HCID 9883512zinc(II)iodideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 203 mg of 4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carbaldehyde (INTERMEDIATE 31) in 2 mL of CH2Cl2 was added 100 μL of TMSCN, and then 1 mg of ZnI2. The mixture was stirred for 30 min at r.t. p-Methoxybenzylamine (157 μL) in 2 mL of MeOH was added and the mixture was heated to reflux for 1.5 h. The reaction mixture was cooled and concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 25M column, eluting with 1 CV of 2% EtOAc in hexanes followed by a linear gradient of 2→100% EtOAc in hexanes over 10 CV to provide the title compound. Mass spectrum (ESI) 487.2 (M+1).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 1.5 h
  4. temperatureThe reaction mixture was cooled
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on a Biotage Horizon, 25M column
  7. washeluting with 1 CV of 2% EtOAc in hexanes

Sources & evidence

ORD record
ord-75e3965bbddd41c9aca7b2868fa2af17
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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