Hydrochloric Acid → HCID 59536664, compound

HRID 1922176Notes

Reaction equation

HRID 1922176 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([CH:13]([O:18][C:19]2[C:20]([CH3:27])=[N:21][C:22]([NH:25][CH3:26])=[CH:23][CH:24]=2)[CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:9]1)=O)(C)(C)C.Cl>>[CH3:27][C:20]1[C:19]([O:18][CH:13]([C@H:10]2[CH2:11][CH2:12][NH:8][CH2:9]2)[CH2:14][CH:15]([CH3:17])[CH3:16])=[CH:24][CH:23]=[C:22]([NH:25][CH3:26])[N:21]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 66737795HCID 66737795, compound

Product 1

HCID 59536664HCID 59536664, compoundYield 12%

Procedure

Stir a mixture of (3S)-3-[1-(2-methyl-6-methylamino-3-pyridyloxy)-3-methyl-butyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (S-2) and aqueous HCl (4M, 0.261 mL, 1.04 mmol) at room temperature for 1 hour. After full conversion, concentrate the mixture, dissolve in dichloromethane and load the mixture onto a pre-packed SCX column. Wash with dichloromethane followed by methanol. Release the product with 2M NH3 in methanol and concentrate under reduced pressure. Purify the crude residue by reverse phase chromatography (17-43% gradient actonitrile in 0.01 M ammoniumformate in water, 85 mL/min, for 8 min., C18 ODB XBridge column, 30×75 mm, 5 μm) to give 9 mg (12%) of (3S)-3-[1-(2-methyl-6-methylamino-3-pyridyloxy)-3-methyl-butyl]-pyrrolidine (S-2). MS (m/z)=278 [M+1].

Workup

  1. concentrationAfter full conversion, concentrate the mixture
  2. dissolutiondissolve in dichloromethane
  3. washWash with dichloromethane
  4. concentrationconcentrate under reduced pressure
  5. customPurify the crude residue by reverse phase chromatography (17-43% gradient actonitrile in 0.01 M ammoniumformate in water, 85 mL/min, for 8 min., C18 ODB XBridge column, 30×75 mm, 5 μm)

Sources & evidence

ORD record
ord-6c61291de4464440a039ad67976ef330
Source dataset
uspto-grants-2012_05
Patent number
US08173821B2

Reaction notes

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