Hydrochloric Acid → (2S)-3-[tert-butoxycarbonyl(methyl)amino]-2-(5-chloro-2-methoxybenzyl)propanoic acid

HRID 80575Notes

Reaction equation

HRID 80575 reaction equation
[H-].[Na+].[CH3:3]I.[C:5]([O:9][C:10]([NH:12][CH2:13][C@H:14]([CH2:18][C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1[O:26][CH3:27])[C:15]([OH:17])=[O:16])=[O:11])([CH3:8])([CH3:7])[CH3:6].Cl>C(OCC)(=O)C.O.O1CCCC1>[C:5]([O:9][C:10]([N:12]([CH3:3])[CH2:13][C@H:14]([CH2:18][C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1[O:26][CH3:27])[C:15]([OH:17])=[O:16])=[O:11])([CH3:8])([CH3:7])[CH3:6]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66935162(2S)-3-[(tert-butoxycarbonyl)amino]-2-(5-chloro-2-methoxybenzyl)propanoic acid

Product 1

HCID 70815183(2S)-3-[tert-butoxycarbonyl(methyl)amino]-2-(5-chloro-2-methoxybenzyl)propanoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a 60% mineral oil dispersion of sodium hydride (1.9 g) in a tetrahydrofuran (50 ml) solution, methyl iodide (2.7 ml) was added under ice cooling, then the (2S)-3-[(tert-butoxycarbonyl)amino]-2-(5-chloro-2-methoxybenzyl)propanoic acid (5 g), described in WO 06-059801A, in a tetrahydrofuran (20 ml) solution was slowly added, then the mixture was stirred at room temperature for 72 hours. To the reaction solution, water (50 ml) and ethyl acetate (20 ml) were added and the layers were separated. The organic layer was extracted with water (20 ml) and was combined with the aqueous layer previously obtained, and acidified (pH2) with 6M hydrochloric acid. This aqueous mixture was extracted with ethyl acetate, then the combined extract was washed with water, saturated aqueous sodium thiosulfate solution, and brine. The organic layer was dried over sodium sulfate, then concentrated to obtain (2S)-3-[tert-butoxycarbonyl(methyl)amino]-2-(5-chloro-2-methoxybenzyl)propanoic acid (5.28 g) (compound S17a).

Workup

  1. additionwas slowly added
  2. customthe layers were separated
  3. extractionThe organic layer was extracted with water (20 ml)
  4. custompreviously obtained
  5. extractionThis aqueous mixture was extracted with ethyl acetate
  6. extractionthe combined extract
  7. washwas washed with water, saturated aqueous sodium thiosulfate solution, and brine
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-892ae960d71a4f4f9320582340aba907
Source dataset
uspto-grants-2014_09
Patent number
US08846660B2

Reaction notes

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