Tetrahydrofuran → Methyl 2-amino-4-{1-[(benzyloxy)carbonyl]-3-piperidinyl}-6-(2-hydroxyphenyl)nicotinate

HRID 412265Notes

Reaction equation

HRID 412265 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[OH:17])[CH:8]=[C:7]([CH:18]2[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])[CH2:19]2)[C:3]=1[C:4]([OH:6])=[O:5].[CH2:34]1COCC1>CO>[NH2:1][C:2]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[OH:17])[CH:8]=[C:7]([CH:18]2[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])[CH2:19]2)[C:3]=1[C:4]([O:6][CH3:34])=[O:5]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 1355506252-Amino-4-{1-[(benzyloxy)carbonyl]-3-piperidinyl}-6-(2-hydroxyphenyl)nicotinic acid

Product 1

HCID 136050638Methyl 2-amino-4-{1-[(benzyloxy)carbonyl]-3-piperidinyl}-6-(2-hydroxyphenyl)nicotinateYield 34%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-amino-4-{1-[(benzyloxy)carbonyl]-3-piperidinyl}-6-(2-hydroxyphenyl)nicotinic acid (1.1 g, 2.5 mmol) in THF (10 mL) and MeOH (5 mL) was added dropwise trimethylsilyldiazomatane (4.0 mL) at room temperature. The reaction mixture was stirred at room temperature for 1.5 hrs, and the reaction was quenched by acetic acid. The mixture was partitioned between ethyl acetate and water. The separated organic phase was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate, 3:1) followed by recrystallization from a mixture of CH2Cl2 and hexane to give methyl 2-amino-4-{1-[(benzyloxy)carbonyl]-3-piperidinyl}-6-(2-hydroxyphenyl)nicotinate as a yellow solid (0.39 g, yield; 34%).

Workup

  1. customthe reaction was quenched by acetic acid
  2. customThe mixture was partitioned between ethyl acetate and water
  3. washThe separated organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (hexane:ethyl acetate, 3:1)
  8. customfollowed by recrystallization from a mixture of CH2Cl2 and hexane

Sources & evidence

ORD record
ord-a5ef30e90f614df5a5e8a1a8ac324270
Source dataset
uspto-grants-2003_05
Patent number
US06562811B1

Reaction notes

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