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

HRID 130785Notes

Reaction equation

HRID 130785 reaction equation
P(=O)(O)(O)O.[C:6]1([CH:12]2[CH2:16][CH2:15][NH:14][CH2:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH:17]([C:19]1[CH:33]=[CH:32][C:22]([O:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=2)=[C:21]([CH3:34])[CH:20]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl.C(OCC)(=O)C>[CH3:34][C:21]1[CH:20]=[C:19]([CH2:17][N:14]2[CH2:15][CH2:16][CH:12]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:13]2)[CH:33]=[CH:32][C:22]=1[O:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][N:25]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 597302456-(4-Formyl-2-methylphenoxy)nicotinonitrile2×HCID 687492483-Phenyl-pyrrolidine phosphoric acid salt

Product 1

HCID 59730246(+/-)-6-[2-Methyl-4-(3-phenyl-pyrolidin-1ylmethyl)-phenoxy]-nicotinonitrileYield 71%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Using a method similar to Example 362, using 3-phenyl-pyrrolidine phosphoric acid salt (1.543 g, 6.29 mmol), 6-(4-formyl-2-methyl-phenoxy)-nicotinonitrile (compound of example 365, step 1) (1.499 g, 6.30 mmol), sodium triacetoxyborohydride (2.00 g, 9.44 mmol), and acetic acid (0.58 mL, 10.1 mmol) in 1,2-dichloroethane (50 mL), after silica gel chromatography (19:1→1:3 hexanes:ethyl acetate) provides 1.65 g (71%) of the title compound as a clear syrup: Mass spectrum (electrospray): m/z=370.1 (M+1); 1H NMR (CDCl3): 8.47 (d, 1H, J=2.4 Hz), 7.91 (dd, 1H, J=2.0, 8.3 Hz), 7.32-7.28 (m, 5H), 7.26-7.17 (m, 2H), 3.67 (s, 2H), 3.45-3.35 (m, 1H), 3.08 (t, 1H, J=9.3 Hz). 2.93-2.85 (m, 1H), 2.72 (dt, 1H, J=5.9, 8.8 Hz), 2.53 (dd, 1H, J=8.3, 9.3 Hz), 2.43-2.32 (m, 1H), 2.14 (s, 3H), 1.99-1.88 (m, 1H).

Sources & evidence

ORD record
ord-24d8e67b0bc341dbbb5d8982cd530fce
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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