Methanol → Ethyl (2S,4S)-4-methyl-3-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl)-1,3-oxazinane-2-carboxylate

HRID 1777384Notes

Reaction equation

HRID 1777384 reaction equation
[NH2:1][C@H:2]([CH3:7])[CH2:3][C:4](O)=[O:5].B.[CH2:9]1[CH2:13][O:12][CH2:11][CH2:10]1.C[OH:15].[CH3:16][C:17]1[CH:18]=[CH:19][C:20]([N:26]2[N:30]=[CH:29][CH:28]=[N:27]2)=[C:21]([CH:25]=1)[C:22]([OH:24])=O>C1COCC1>[CH3:7][C@H:2]1[CH2:3][CH2:4][O:5][C@@H:10]([C:11]([O:12][CH2:13][CH3:9])=[O:15])[N:1]1[C:22](=[O:24])[C:21]1[CH:25]=[C:17]([CH3:16])[CH:18]=[CH:19][C:20]=1[N:26]1[N:30]=[CH:29][CH:28]=[N:27]1

Participants

6

Reactant 4

HCID 887MethanolHCID 2723981Borane;tetrahydrofuranHCID 5706670(R)-3-aminobutanoic acidHCID 532601655-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid

Product 1

HCID 118030914Ethyl (2S,4S)-4-methyl-3-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl)-1,3-oxazinane-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3R)-3-aminobutanoic acid (1.0 g, 9.7 mmol) in THF (10 mL), a solution of borane-THF in 0.9 mol/L (32.3 mL, 29.1 mmol) was added dropwise under cooling in an ice bath over a period of 1 hour, and the resulting mixture was stirred for 20 minutes at room temperature. The resulting mixture was heated to 80° C. and further stirred with heating for 6 hours. Methanol was added thereto under cooling in an ice bath, the reaction mixture was stirred for 30 minutes and then concentrated under reduced pressure. By using the obtained (3R)-3-aminobutan-1-ol, ethyl glyoxylate (polymer type, a solution of 47% toluene) (2.0 mL, 9.7 mmol) and 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid (0.50 g, 2.5 mmol), the same procedure as in Reference Example 1 was carried out to obtain a diastereomer mixture (colorless oil). The obtained diastereomer mixture was purified by column chromatography (HP-Sil 10 g, hexane/EtOAc=90/10 to 0/100) to obtain the title compound (0.37 g), which was a low polar compound (colorless oil).

Workup

  1. temperatureunder cooling in an ice bath over a period of 1 hour
  2. temperatureThe resulting mixture was heated to 80° C.
  3. stirringfurther stirred
  4. temperaturewith heating for 6 hours
  5. temperatureunder cooling in an ice bath
  6. stirringthe reaction mixture was stirred for 30 minutes
  7. concentrationconcentrated under reduced pressure
  8. customto obtain a diastereomer mixture (colorless oil)
  9. customThe obtained diastereomer mixture was purified by column chromatography (HP-Sil 10 g, hexane/EtOAc=90/10 to 0/100)

Sources & evidence

ORD record
ord-e32bc29a0c5e483788ab6d9748c980c2
Source dataset
uspto-grants-2016_02
Patent number
US09266870B2

Reaction notes

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