Hydrochloric Acid → ((R)-2-carbamoyl-propyl)-carbamic acid tert-butyl ester

HRID 246125Notes

Reaction equation

HRID 246125 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C@@H:10]([CH3:14])[C:11](O)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:16](C)CCCN=C=NCC.ON1C(=O)CCC1=O.[OH-].[NH4+].Cl>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C@H:10]([C:11](=[O:12])[NH2:16])[CH3:14])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 80170N-HydroxysuccinimideHCID 11041840(R)-3-((tert-butoxycarbonyl)amino)-2-methylpropanoic acid

Product 1

HCID 22845901((R)-2-carbamoyl-propyl)-carbamic acid tert-butyl esterYield 72%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(R)-3-(tert-Butoxycarbonylamino)-2-methylpropanoic acid (465 mg, 2.3 mmol) was dissolved in dichloromethane (11 ml). 4-Dimethylaminopyridine (280 mg, 2.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (877 mg, 4.58 mmol) were added, followed by N-hydroxysuccinimide (290 mg, 2.52 mmol). After 4 h of stirring at room temperature, concentrated ammonium hydroxide (1.6 ml) was added slowly. The reaction mixture was stirred for an additional 20 min then aqueous HCl and ethyl acetate were added and the aqueous layer was extracted six times with ethyl acetate. The combined organic layers were washed with sodium bicarbonate solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography to give 335 mg (72%) of ((R)-2-carbamoyl-propyl)-carbamic acid tert-butyl ester. (M+Na)+=225.

Workup

  1. stirringThe reaction mixture was stirred for an additional 20 min
  2. extractionthe aqueous layer was extracted six times with ethyl acetate
  3. washThe combined organic layers were washed with sodium bicarbonate solution
  4. dry with materialdried over sodium sulfate
  5. customAfter evaporation
  6. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f28b6b3edde042c796bb9ce5b567ae25
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…