Lithium hydroxide, monohydrate → HCID 89387517, compound

HRID 1913515Notes

Reaction equation

HRID 1913515 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH:12]([C:17]([O:19]C)=[O:18])[C:13]([O:15][CH3:16])=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>CO.O>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH:12]([C:13]([O:15][CH3:16])=[O:14])[C:17]([OH:19])=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86675824HCID 86675824, compound

Product 1

HCID 89387517HCID 89387517, compoundYield 77.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

To dimethyl malonate (102 mL), a solution of sodium methoxide in methanol (28%, 90.4 mL) was added at room temperature, and the mixture was stirred at 60° C. for 30 minutes. The white suspension was cooled to room temperature. Then, tert-butyl (3-bromopropyl)carbamate (106 g) was added thereto at once, and the mixture was stirred at room temperature for 12 hours. To the reaction solution, water was added, and organic matter was extracted with diethyl ether. The organic layer was washed with a 1 N aqueous sodium hydroxide and saturated sodium chloride solution in this order, then dried over anhydrous sodium sulfate, and filtered, and the solvent was distilled off under reduced pressure to obtain a crude product of dimethyl {3-[(tert-butoxycarbonyl)amino]propyl}malonate. The obtained ester (94 g) was dissolved in methanol (100 mL). To the solution, a solution of lithium hydroxide monohydrate (13.6 g) in water (300 mL) and methanol (300 mL) was added at 0° C., and the mixture was stirred at room temperature for 15 hours. Methanol was distilled off under reduced pressure, and organic matter was extracted with ethyl acetate. 2 N hydrochloric acid (160 mL) was added to the aqueous layer, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, then dried over anhydrous sodium sulfate, and filtered, and the solvent was distilled off under reduced pressure to obtain a crude product. This crude product was purified by silica gel column chromatography (eluting solvent: methylene chloride-methylene chloride/methanol=10/1) to obtain the title compound (69.1 g).

Workup

  1. distillationMethanol was distilled off under reduced pressure, and organic matter
  2. extractionwas extracted with ethyl acetate
  3. addition2 N hydrochloric acid (160 mL) was added to the aqueous layer
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with saturated sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. distillationthe solvent was distilled off under reduced pressure
  9. customto obtain a crude product
  10. customThis crude product was purified by silica gel column chromatography (eluting solvent: methylene chloride-methylene chloride/methanol=10/1)

Sources & evidence

ORD record
ord-418215c6ea53466e800a3cb661ec1341
Source dataset
uspto-grants-2013_12
Patent number
US08609710B2

Reaction notes

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