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

HRID 1096177Notes

Reaction equation

HRID 1096177 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+].CC(O)=O.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O>[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 RT (IPC by GC). A solution of 2 ml (0.64 eq.) AcOH in 15 ml toluene was added. After 30 min at RT, the reaction mixture was cooled to 0° C. and 100 ml sat. aq. NaHCO3 solution was added over 40 min (foaming). 50 ml EtOAc were added. The mixture was stirred for 30 min at RT. The mixture was extracted with 200 ml and a second time with 50 ml EtOAc. The organic phases were washed with 50 ml sat. aq. NaHCO3 solution followed by 50 ml sat. aq. NaCl solution. The organic phases were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 21.5 g of the title compound as an oil (ca. 95% yield, corrected for ca 3% residual toluene and 3% amine starting material).

Workup

  1. waitAfter 30 min at RT
  2. temperaturethe reaction mixture was cooled to 0° C.
  3. stirringThe mixture was stirred for 30 min at RT
  4. extractionThe mixture was extracted with 200 ml
  5. washThe organic phases were washed with 50 ml sat. aq. NaHCO3 solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a95241a4b9f043fa949b8725e89cf221
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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