Hydrochloric Acid → HCID 66734753, compound

HRID 1963503Notes

Reaction equation

HRID 1963503 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH:10]([C:24]2[N:28]([CH3:29])[N:27]=[N:26][N:25]=2)[CH2:9]1)=[O:7])C.[OH-].[Na+].[NH2:33]O.Cl>CO.O>[CH3:29][N:28]1[C:24]([CH:10]2[CH2:9][CH:8]([C:6]3[O:7][NH:33][C:4](=[O:3])[CH:5]=3)[CH2:13][CH2:12][N:11]2[C:14]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])=[N:25][N:26]=[N:27]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 66734816HCID 66734816, compound

Product 1

HCID 66734753HCID 66734753, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-40 °C

Procedure

Benzyl 4-(3-ethoxy-3-oxopropanoyl)-2-(1-methyl-1H-tetrazol-5-yl)piperidine-1-carboxylate (0.947 g, 2.28 mmol) was dissolved in MeOH (10 mL) and cooled to −40° C. 3.8 M NaOH (0.600 mL, 2.28 mmol) dissolved in water (1 mL) was added and the reaction stirred at −40° C. for 40 min. Hydroxylamine (50% by weight in water, 0.140 mL, 2.28 mmol) was added and stirring continued for 3.5 h at −40° C. The reaction mixture was then added to a preheated 80° C. warm solution of 6 M HCl (11.40 mL, 68.38 mmol) and stirred for 20 min. The reaction mixture was partitioned between water and DCM. The aqueous phase was extracted twice with DCM and the combined organic phase was dried and evaporated. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 15-55% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. Benzyl 2-(1-methyl-1H-tetrazol-5-yl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (488 mg, 56%) was isolated. 1H NMR (400 MHz, cdcl3) δ 1.86-1.99 (m, 1H), 2.18-2.30 (m, 1H), 2.33-2.54 (m, 2H), 3.01-3.12 (m, 1H), 3.78-4.09 (m, 5H), 5.05 (s, 2H), 5.20-5.30 (m, 1H), 5.67 (s, 1H), 7.20-7.27 (m, 2H), 7.27-7.39 (m, 3H). MS m/z 385 (M+H)+

Workup

  1. additionwas added
  2. stirringstirring
  3. waitcontinued for 3.5 h at −40° C
  4. additionThe reaction mixture was then added to a preheated 80° C.
  5. stirringstirred for 20 min
  6. customThe reaction mixture was partitioned between water and DCM
  7. extractionThe aqueous phase was extracted twice with DCM
  8. customthe combined organic phase was dried
  9. customevaporated
  10. customThe compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm)
  11. custombuffer over 20 minutes

Sources & evidence

ORD record
ord-14f00c3ab79d4b6a9df27bc765c021d7
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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