4-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-3-nitro-benzoic acid methyl ester → 3-amino-4-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-benzoic acid methyl ester

HRID 1987357Notes

Reaction equation

HRID 1987357 reaction equation
[CH3:1][O:2][C:3](=[O:34])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[CH:16]([C:17]3[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=3)[CH2:15][CH2:14][CH2:13][CH:12]2[C:24]2[C:29]([CH3:30])=[CH:28][CH:27]=[CH:26][N:25]=2)=[C:6]([N+:31]([O-])=O)[CH:5]=1>CO.CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3](=[O:34])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[CH:12]([C:24]3[C:29]([CH3:30])=[CH:28][CH:27]=[CH:26][N:25]=3)[CH2:13][CH2:14][CH2:15][CH:16]2[C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)=[C:6]([NH2:31])[CH:5]=1

Participants

5

Reactant 1

HCID 674219694-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-3-nitro-benzoic acid methyl ester

Product 1

HCID 674211763-amino-4-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-benzoic acid methyl esterYield 69%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Using General Procedure A: A solution of 3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (0.829 g, 3.10 mmol), 4-bromomethyl-3-nitrobenzoic acid methyl ester (1.26 g, 4.61 mmol), KI (115 mg, 0.69 mmol), and DIPEA (1.20 mL, 6.89 mmol) in DMF (16 mL) was heated at 60° C. for 18 hours. Purification of the crude material by column chromatography on silica gel (40:1:1 CH2Cl2—CH3OH—NH4OH) provided 1.40 g (98%) of 4-3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-3-nitro-benzoic acid methyl ester as a tan solid. To a solution of 4-(3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-3-nitro-benzoic acid methyl ester (1.40 g,3.03 mmol) in MeOH (15 mL) and EtOAc (15 mL) was added palladium (50% wet with water), 10 wt. % on activated carbon (0.30 g). The resultant mixture was hydrogenated at 30 psi on a Parr shaker for 3 hours. The mixture was vacuum filtered through celite and the cake was washed with MeOH and EtOAc. The solvent was removed from the filtrate under reduced pressure and the thus obtained oil was purified by column chromatography on silica gel (40:1:1 CH2Cl2—CH3OH—NH4OH) and provided 0.90 g (69%) of 3-amino-4-(3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-benzoic acid methyl ester.

Workup

  1. filtrationfiltered through celite
  2. washthe cake was washed with MeOH and EtOAc
  3. customThe solvent was removed from the filtrate under reduced pressure
  4. customthe thus obtained oil was purified by column chromatography on silica gel (40:1:1 CH2Cl2—CH3OH—NH4OH)

Sources & evidence

ORD record
ord-9124d13313f3438faf2c37a5e1c4e016
Source dataset
uspto-grants-2009_06
Patent number
US07550484B2

Reaction notes

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