Hydrochloric Acid → methyl 2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)-amino]-3-methylbutanoate hydrochloride

HRID 2209715Notes

Reaction equation

HRID 2209715 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][C@H:13]([CH:18]([CH3:20])[CH3:19])[C:14]([O:16][CH3:17])=[O:15])(=[O:11])=[O:10])=[CH:5][CH:4]=1.Cl.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][Cl:29])[CH:23]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O.C(OCC)(=O)C>[ClH:29].[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]([CH2:28][C:24]2[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=2)[C@H:13]([CH:18]([CH3:20])[CH3:19])[C:14]([O:16][CH3:17])=[O:15])(=[O:10])=[O:11])=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium Carbonate2×HCID 233943-(Chloromethyl)pyridine hydrochloride2×HCID 10946547methyl 2(R)-[[4-methoxybenzenesulfonyl]amino]-3-methylbutanoate

Product 1

HCID 22856285methyl 2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)-amino]-3-methylbutanoate hydrochloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 2(R)-[[4-methoxybenzenesulfonyl]amino]-3-methylbutanoate (1662 g, 5.52 mol) in dimethylformamide (10.9 L) is added 3-picolyl chloride hydrochloride (947.3 g, 5.77 mol) followed by powdered potassium carbonate (2409.9 g, 17.36 mol). The reaction mixture is stirred at room temperature for 2 days. At that time, additional quantities of 3-picolyl chloride hydrochloride (95 g) and powdered potassium carbonate (241 g) are added, and the reaction is stirred for 3 more days. The solids are then filtered away, the crude product is poured into water (22 L), and the pH is adjusted to pH=8 with 6N sodium hydroxide. This solution is extracted well with toluene (4×10 L), the combined organic layers are washed with water (2×12 L), and then with 6N hydrochloric acid (3×1600 mL). This aqueous layer is then re-adjusted to pH=8 with 6N sodium hydroxide, extracted with toluene (4×10 L), dried (Na2SO4), and the solvent is evaporated. The oil obtained is re-dissolved in ethyl acetate (12 L), cooled to 5° C., and to this is added methanolic HCl (834 mL). After stirring for 2 hours, the precipitated product is collected by filtration to give methyl 2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3-methylbutanoate hydrochloride.

Workup

  1. stirringthe reaction is stirred for 3 more days
  2. filtrationThe solids are then filtered away
  3. additionthe crude product is poured into water (22 L)
  4. extractionThis solution is extracted well with toluene (4×10 L)
  5. washthe combined organic layers are washed with water (2×12 L)
  6. extractionre-adjusted to pH=8 with 6N sodium hydroxide, extracted with toluene (4×10 L)
  7. dry with materialdried (Na2SO4)
  8. customthe solvent is evaporated
  9. customThe oil obtained
  10. temperaturecooled to 5° C.
  11. stirringAfter stirring for 2 hours
  12. filtrationthe precipitated product is collected by filtration

Sources & evidence

ORD record
ord-e6a7ee78b69b43fc967f5511f78451b6
Source dataset
uspto-grants-1995_10
Patent number
US05455258

Reaction notes

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