Acetic Acid → (+/-)-6-[2-Methyl-4-(3-phenyl-azepan-1ylmethyl)-phenoxy]-nicotinonitrile

HRID 130786Notes

Reaction equation

HRID 130786 reaction equation
[C:1]1([CH:7]2[CH2:13][CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:14]([C:16]1[CH:30]=[CH:29][C:19]([O:20][C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=2)=[C:18]([CH3:31])[CH:17]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl.C(OCC)(=O)C.CO>[CH3:31][C:18]1[CH:17]=[C:16]([CH2:14][N:9]2[CH2:10][CH2:11][CH2:12][CH2:13][CH:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:8]2)[CH:30]=[CH:29][C:19]=1[O:20][C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 236263713-PhenylazepaneHCID 597302456-(4-Formyl-2-methylphenoxy)nicotinonitrile2×

Product 1

HCID 59730323(+/-)-6-[2-Methyl-4-(3-phenyl-azepan-1ylmethyl)-phenoxy]-nicotinonitrileYield 66.1%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Using a method similar to Example 365 step 2, using 3-phenyl-azapane (0.0610 g, 0.348 mmol), 6-(4-formyl-2-methyl-phenoxy)-nicotinonitrile (compound of example 365 step 1) (0.0816 g, 0.342 mmol), sodium triacetoxyborohydride (0.110 g, 0.519 mmol), and acetic acid (0.032 mL, 0.56 mmol) in 1,2-dichloroethane (4.0 mL), (no aqueous work-up) provides, after ion exchange chromatography (methanol→2 M ammonia/methanol) and silica gel chromatography (4:1→1:1 hexanes:ethyl acetate), 0.0899 g (65%) of the title compound as a yellow oil: Mass spectrum (electrospray): m/z=398.2 (M+1).

Workup

  1. custom(no aqueous work-up) provides

Sources & evidence

ORD record
ord-9f300b21c8a64fb7af06b7e964d6ed6d
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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