Benzyl chloroformate → 1-Benzyl 3-tert-butyl 1,3-pyrazolidinedicarboxylate

HRID 1396849Notes

Reaction equation

HRID 1396849 reaction equation
[NH:1]1[CH:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:4][CH:3]=[N:2]1.C([BH3-])#N.[Na+].[CH:17]1[CH:22]=[CH:21][C:20]([CH2:23][O:24][C:25](Cl)=[O:26])=[CH:19][CH:18]=1>C(O)(=O)C>[N:2]1([C:25]([O:24][CH2:23][C:20]2[CH:21]=[CH:22][CH:17]=[CH:18][CH:19]=2)=[O:26])[CH2:3][CH2:4][CH:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[NH:1]1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 5003444Sodium cyanoborohydrideHCID 86706338tert-butyl 4,5-dihydro-1H-pyrazole-5-carboxylate

Product 1

HCID 133415401-Benzyl 3-tert-butyl 1,3-pyrazolidinedicarboxylateYield 62.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 1,1-dimethylethyl 4,5-dihydro-1H-pyrazole-5-carboxylate (5 g, 29.4 mmol) dissolved in acetic acid (75 mL) was added sodium cyanoborohydride (3.69 g, 58.8 mmol) over 10 minutes. After 30 min. the reaction mixture was concentrated. The intermediate was diluted with ethyl acetate and basified with sat. Na2CO3. The ethyl acetate was dried over sodium sulfate, filtered, and concentrated. The intermediate was diluted with tetrahydrofuran (THF) (75 mL), and triethylamine was added (8.19 mL, 58.8 mmol), followed by Cbz-Cl (2.1 mL, 14.69 mmol). After 2 h, the organic salts were filtered and the crude product was purified by silica gel column using 20-80% EtOAc/hexanes to afford 2.8 g (9.14 mmol) of 3-(1,1-dimethylethyl) 1-(phenylmethyl) 1,3-pyrazolidinedicarboxylate. LC-MS (ES) m/e 307.0 (M+H)+.

Workup

  1. concentrationAfter 30 min. the reaction mixture was concentrated
  2. additionThe intermediate was diluted with ethyl acetate and basified with sat. Na2CO3
  3. dry with materialThe ethyl acetate was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe intermediate was diluted with tetrahydrofuran (THF) (75 mL), and triethylamine
  7. additionwas added (8.19 mL, 58.8 mmol)
  8. filtrationthe organic salts were filtered
  9. customthe crude product was purified by silica gel column

Sources & evidence

ORD record
ord-4c5479cb6874406b8589312dda7b85f6
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

Loading…