Acetic Acid → 1-[2-(Benzyl-tert-butoxycarbonylmethyl-amino)-ethyl]-cyclopropanecarboxylic acid tert-butyl ester

HRID 2095467Notes

Reaction equation

HRID 2095467 reaction equation
[C:1]([O:5][C:6]([C:8]1([CH2:11][CH:12]=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:14]([O:18][C:19](=[O:29])[CH2:20][NH:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([CH3:17])([CH3:16])[CH3:15].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:5][C:6]([C:8]1([CH2:11][CH2:12][N:21]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:20][C:19]([O:18][C:14]([CH3:17])([CH3:15])[CH3:16])=[O:29])[CH2:9][CH2:10]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 11020442Tert-butyl 2-(benzylamino)acetateHCID 58817571Tert-Butyl 1-(2-oxoethyl)cyclopropanecarboxylate

Product 1

HCID 667829971-[2-(Benzyl-tert-butoxycarbonylmethyl-amino)-ethyl]-cyclopropanecarboxylic acid tert-butyl esterYield 100.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

10.5 g (54.7 mmol, 1 eq.) 1-(2-oxo-ethyl)-cyclopropanecarboxylic acid tert-butyl ester and 13.21 g (1.08 eq.) N-benzylglycine tert-butyl ester were dissolved in 140 ml toluene. 21 g (1.63 eq.) sodium triacetoxyborohydride were added (exotherm from 25° C. to 28° C.) and the reaction mixture was stirred 5 h at room temperature (IPC by GC). A solution of 2 ml (0.64 eq.) acetic acid in 15 ml toluene was added. After 30 min at room temperature, the reaction mixture was cooled to 0° C. and 100 ml sat. aq. sodium hydrogencarbonate solution was added over 40 min (foaming). 50 ml ethyl acetate were added. The mixture was stirred for 30 min at room temperature. The mixture was extracted with 200 ml and a second time with 50 ml ethyl acetate. The organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution followed by 50 ml sat. aq. sodium chloride solution. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 21.5 g of the titled compound as an oil (ca. 95% yield, corrected for ca 3% residual toluene and 3% amine starting material).

Workup

  1. waitAfter 30 min at room temperature
  2. temperaturethe reaction mixture was cooled to 0° C.
  3. stirringThe mixture was stirred for 30 min at room temperature
  4. extractionThe mixture was extracted with 200 ml
  5. washThe organic phases were washed with 50 ml sat. aq. sodium hydrogencarbonate solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cd3cb18552644802a9a81f059326da86
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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