Methylamine → (2S,5S)-tert-Butyl 5-hydroxy-2-(methoxymethyl)-4-(methylcarbamoyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 627264Notes

Reaction equation

HRID 627264 reaction equation
C[Al](C)C.[CH3:5][NH2:6].[OH:7][C@@H:8]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([CH2:21][O:22][CH3:23])[CH:10]=[C:9]1[C:24]([O:26]C)=O>C1(C)C=CC=CC=1>[OH:7][C@@H:8]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([CH2:21][O:22][CH3:23])[CH:10]=[C:9]1[C:24](=[O:26])[NH:6][CH3:5]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 16682925TrimethylaluminumHCID 89852057(2S,5S)-1-tert-butyl 4-methyl 5-hydroxy-2-(methoxymethyl)-5,6-dihydropyridine-1,4(2H)-dicarboxylate2×

Product 1

HCID 89863096(2S,5S)-tert-Butyl 5-hydroxy-2-(methoxymethyl)-4-(methylcarbamoyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 53.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-10 °C

Procedure

A dry 2 necked round bottomed flask was equipped with a magnetic stirrer and it was flushed with nitrogen twice. Then trimethylaluminum (0.191 ml, 0.38 mmol) was added followed by toluene (0.5 ml). The solution was cooled down to −10° C. and methanamine (0.183 ml, 0.37 mmol) was added slowly. The reaction mixture was stirred at that temperature for 20 minutes. A solution of (2S,5S)-1-tert-butyl 4-methyl 5-hydroxy-2-(methoxymethyl)-5,6-dihydropyridine-1,4(2H)-dicarboxylate (Intermediate 254, 100 mg, 0.33 mmol) in toluene (0.5 ml) was added slowly at room temperature. After stirring overnight the reaction was quenched with 1M HCl and allowed to stir for 15 minutes to complete the hydrolysis. The reaction mixture was extracted with ethyl acetate. The organics were washed with saturated sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (MeOH/DCM) afforded the title compound as a clear oil (53 mg).

Workup

  1. customA dry 2 necked round bottomed flask
  2. customwas equipped with a magnetic stirrer
  3. customit was flushed with nitrogen twice
  4. stirringAfter stirring overnight the reaction
  5. customwas quenched with 1M HCl
  6. stirringto stir for 15 minutes
  7. customthe hydrolysis
  8. extractionThe reaction mixture was extracted with ethyl acetate
  9. washThe organics were washed with saturated sodium bicarbonate
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-f98b194d5d8f4d25aea6c35c7e6e2e86
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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