Hydrochloric Acid → HCID 68500267, compound

HRID 1963344Notes

Reaction equation

HRID 1963344 reaction equation
[CH2:1]([C@H:8]1[CH2:13][C@H:12]([C:14](=[O:21])[CH2:15][C:16](OCC)=[O:17])[CH2:11][CH2:10][N:9]1[C:22]([O:24][CH3:25])=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].Cl.[NH2:29]O.Cl>CO.CO.O.O>[CH3:25][O:24][C:22]([N:9]1[CH2:10][CH2:11][C@@H:12]([C:14]2[O:21][NH:29][C:16](=[O:17])[CH:15]=2)[CH2:13][C@@H:8]1[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:23]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 443297Hydroxyamine hydrochlorideHCID 131730369HCID 131730369, compound

Product 1

HCID 68500267HCID 68500267, compoundYield 54.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

A solution of trans-methyl 2-benzyl-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (6.35 g, 18.3 mmol) in MeOH (2 mL) was added to a solution of NaOH (0.77 g, 19.4 mmol) in MeOH/H2O (15 mL/0.9 mL) at −30° C. After 10 minutes was added a solution of hydroxylamine hydrochloride (2.54 g, 36.6 mmol) and NaOH (1.46 g, 36.6 mmol) in MeOH (18 mL) and H2O (18 mL). Stirring was continued at −30° C. for 30 minutes. The reaction mixture was then poured into concentrated HCl (20 mL) held at 80° C. The solution was stirred for 30 minutes. The organic solvent was evaporated and the aqueous phase extracted with DEE (×3). The organic phase was dried over Na2SO4 and evaporated to give a solid, 3.68 g, which was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 20-70% acetonitrile in H2O/MeCN/FA 95/5/0.2 buffer, over 18 minutes with a flow of 19 mL/minutes. Trans-methyl-2-benzyl-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (2.54 g, 54.6%) was isolated as a solid. 1H NMR (600 MHz, cdcl3) δ 1.50-2.21 (m, 4H), 2.91 (m, 2H), 3.10 (m, 2H), 3.58 (d, 3H), 4.04-4.41 (m, 1H), 4.43-4.82 (m, 1H), 5.55-5.84 (m, 1H), 7.15-7.30 (m, 5H); MS m/z 317 (M+H)+.

Workup

  1. customheld at 80° C
  2. stirringThe solution was stirred for 30 minutes
  3. customThe organic solvent was evaporated
  4. extractionthe aqueous phase extracted with DEE (×3)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. customevaporated
  7. customto give a solid, 3.68 g, which
  8. customwas purified by preparative HPLC on a Kromasil C8 column (10 μm 250×20 ID mm)
  9. waitover 18 minutes with a flow of 19 mL/minutes

Sources & evidence

ORD record
ord-ddb6bf1da6e347dfae40501ca52ec9da
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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