Hydrochloric Acid → HCID 10988154, compound

HRID 1867672Notes

Reaction equation

HRID 1867672 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C@H:11]([C:15]([OH:17])=[O:16])[CH2:12][O:13][CH3:14])=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH:18]1(NC2CCCCC2)CCCCC1.O.COS(OC)(=O)=O.[OH-].[NH4+].Cl>CCCC(C)C.O1CCCC1>[C:3]([O:7][C:8]([N:10]([CH3:18])[C@H:11]([C:15]([OH:17])=[O:16])[CH2:12][O:13][CH3:14])=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 962WaterHCID 6497Dimethyl SulfateHCID 7582DicyclohexylamineHCID 14923Ammonium HydroxideHCID 24758Sodium hydrideHCID 7016354(2S)-2-(((tert-butoxy)carbonyl)amino)-3-methoxypropanoic acid

Product 1

HCID 10988154HCID 10988154, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 78922-MethylpentaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (2.1 g, 52.4 mmol) was washed with iso-hexane under a nitrogen atmosphere. Tetrahydrofuran (20 ml) was added and the suspension cooled in an ice/water bath. A mixture of N-(tert-butoxycarbonyl)-O-methyl-L-serine (starting material obtained by converting the dicyclohexylamine salt to the free base as described above in the pre-amble to the Examples) (2.5 g, 11.4 mmol) and water (41 μl, 2.28 mmol) in tetrahydrofuran (15 ml) was slowly added. The resulting mixture was allowed to stir for 20 minutes and dimethylsulfate (3.3 ml, 35.3 mmol) was slowly added. The mixture was stirred for 2 hours and treated with concentrated ammonium hydroxide (15 ml). The resulting mixture was stirred for a further 2 hours, then acidified with 2M hydrochloric acid, extracted with ethyl acetate, dried (MgSO4) and concentrated under reduced pressure. The residues were dissolved in methanol, absorbed onto an NH2 column, washed with methanol and eluted with 7N ammonia in methanol. Appropriate fractions were combined and evaporated under reduced pressure to give N-(tert-butoxycarbonyl)-N,O-dimethyl-L-serine (1.5 g, 56%) as a viscous, colourless oil; 1H NMR spectrum: (DMSO d6, 100° C.) 1.40 (s, 9H), 2.77 (s, 3H), 3.26 (s, 3H), 3.67 (m, 2H), 4.51 (m, 1H).

Workup

  1. temperaturethe suspension cooled in an ice/water bath
  2. customobtained
  3. additionwas slowly added
  4. stirringThe mixture was stirred for 2 hours
  5. stirringThe resulting mixture was stirred for a further 2 hours
  6. extractionextracted with ethyl acetate
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residues were dissolved in methanol
  10. customabsorbed onto an NH2 column
  11. washwashed with methanol
  12. washeluted with 7N ammonia in methanol
  13. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-75ca4a4fe03d41008872e431b513f9d6
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

Loading…