Hydrochloric Acid → HCID 66741776, compound

HRID 1963395Notes

Reaction equation

HRID 1963395 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6]([C@H:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH3:17])=[O:15])[C@@H:10]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:31]O.Cl>CO.O.C(Cl)Cl>[CH3:27][S:24]([C:21]1[CH:22]=[CH:23][C:18]([C@H:10]2[CH2:9][C@@H:8]([C:6]3[O:7][NH:31][C:4](=[O:3])[CH:5]=3)[CH2:13][CH2:12][N:11]2[C:14]([O:16][CH3:17])=[O:15])=[CH:19][CH:20]=1)(=[O:26])=[O:25]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 131730395HCID 131730395, compound

Product 1

HCID 66741776HCID 66741776, compoundYield 49.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(methylsulfonyl)phenyl)piperidine-1-carboxylate (2.6 g, 6.32 mmol) was suspended in MeOH (100 mL). DCM (40 mL) was added and the reaction cooled to −40° C. 3.8 M sodium hydroxide (1.663 mL, 6.32 mmol) in water (10.00 mL) was added and the reaction stirred at −40° C. for 20 min. Hydroxylamine (50% in water, 0.387 mL, 6.32 mmol) was added and the reaction stirred at −40° C. for 3 h. The reaction mixture was then added to a prewarmed 80° C. solution of 6 M hydrogen chloride (63.2 mL, 379.13 mmol) and the reaction stirred for 30 min. The solvent was evaporated in vacuo. DCM (250 mL) and water (250 mL) were added, shaken and the phases separated. The organic phase was dried with a phase separator and evaporated in vacuo. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 15-45% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. Cis-methyl 2-(4-(methylsulfonyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.200 g, 49.9%) was isolated as a white solid. 1H NMR (600 MHz, cdcl3) δ 1.85-1.91 (m, 1H), 2.18-2.29 (m, 2H), 2.35-2.41 (m, 1H), 2.98 (s, 3H), 3.00-3.13 (m, 1H), 3.38-3.44 (m, 1H), 3.67 (s, 3H), 4.13-4.19 (m, 1H), 5.20 (t, 1H), 5.47 (s, 1H), 7.34 (d, 2H), 7.83 (d, 2H). MS m/z 381 (M+H)+

Workup

  1. stirringthe reaction stirred at −40° C. for 3 h
  2. stirringthe reaction stirred for 30 min
  3. customThe solvent was evaporated in vacuo
  4. additionDCM (250 mL) and water (250 mL) were added
  5. stirringshaken
  6. customthe phases separated
  7. customThe organic phase was dried with a phase separator
  8. customevaporated in vacuo
  9. customThe compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm)
  10. custombuffer over 30 minutes

Sources & evidence

ORD record
ord-6f5bb35e148f47958d36781a9ef7ffcc
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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