Hydrochloric Acid → HCID 68503570, compound

HRID 1963346Notes

Reaction equation

HRID 1963346 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>[CH2:1]([C@H:8]1[CH2:13][C@@H:12]([C:14]2[O:21][NH:29][C:16](=[O:17])[CH:15]=2)[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

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 443297Hydroxyamine hydrochlorideHCID 131730370HCID 131730370, compound

Product 1

HCID 68503570HCID 68503570, compound

Reagents, catalysts & solvents 3

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

Procedure

A solution of cis-methyl 2-benzyl-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (2.15 g, 6.18 mmol) (from Example 1, Step 1) in MeOH (0.75 mL) was added to a solution of NaOH (0.26 g, 6.55 mmol) in MeOH/H2O (5 mL/0.3 mL) at −30° C. After 10 minutes was added a solution of hydroxylamine hydrochloride (0.86 g, 12.4 mmol) and NaOH (0.49 g, 12.4 mmol) in MeOH (6.1 mL) and H2O (6.1 mL). Stirring was continued at −30° C. for 30 minutes. The reaction mixture was then poured into concentrated HCl (7 mL) held at 80° C. The solution was stirred for 30 minutes. The organic solvent was evaporated and the aqueous phase extracted with ether (×3). The combined organic phases were dried over Na2SO4, and evaporated to yield a solid, 2.2 g. The compound 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. The title compound was isolated (1.1 g, 57%). 1H NMR (600 MHz, cdcl3) δ 1.76-2.15 (m, 4H), 2.63 (m, 1H), 2.82 (m, 1H), 2.87-3.03 (m, 1H), 3.03-3.22 (m, 1H), 3.61 (s, 3H), 3.99 (m, 1H), 4.19-4.33 (m, 1H), 5.71 (s, 1H), 7.01-7.37 (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 ether (×3)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. customevaporated
  7. customto yield a solid, 2.2 g
  8. customThe compound was 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-d0d15daca5cd4519ac8317c349f0a45a
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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