4-Chlorobenzylamine → 2-(4-Chloro-benzylamino)-cyclopent-1-enecarboxylic acid ethyl ester

HRID 731382Notes

Reaction equation

HRID 731382 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH2:8][C:7]1=O)=[O:5])[CH3:2].[Cl:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][NH2:18])=[CH:15][CH:14]=1.C([BH3-])#N.[Na+]>C(O)C.C(O)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH2:10][CH2:9][CH2:8][C:7]=1[NH:18][CH2:17][C:16]1[CH:19]=[CH:20][C:13]([Cl:12])=[CH:14][CH:15]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 660364-ChlorobenzylamineHCID 69136Ethyl 2-oxocyclopentanecarboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 576712342-(4-Chloro-benzylamino)-cyclopent-1-enecarboxylic acid ethyl esterYield 55.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 2-oxo-cyclopentanecarboxylic acid ethyl ester (3.00 g, 19.2 mmol) in ethanol (20 mL) was treated with 4-chlorobenzylamine (2.72 g, 19.2 mmol), sodium cyanoborohydride (2.42 g, 38.4 mmol), and glacial acetic acid (10 drops) and stirred for 16 h at 50° C. After cooling to 25° C. the solvent was removed in vacuo, the crude material was redissolved in ethyl acetate (100 mL) and washed with saturated aqueous sodium bicarbonate solution (100 mL). The aqueous layer was discarded and the organic layer was washed with 1.0 M aqueous hydrochloric acid solution (50 mL). The organic layer was discarded, 1.0 M aqueous sodium hydroxide solution (75 mL) was added and the aqueous layer was extracted with ethyl acetate (100 mL). The organic layer was dried over sodium sulfate, filtered and the solvent was removed in vacuo to afford the crude product, 2-(4-chloro-benzylamino)-cyclopent-1-enecarboxylic acid ethyl ester (2.98 g, 10.68 mmol, 55.6%), as a light yellow oil. LC-MS (ESI) calcd for C15H18ClNO2 279.10, found 280.1 [M+H+].

Workup

  1. temperatureAfter cooling to 25° C. the solvent
  2. customwas removed in vacuo
  3. dissolutionthe crude material was redissolved in ethyl acetate (100 mL)
  4. washwashed with saturated aqueous sodium bicarbonate solution (100 mL)
  5. washthe organic layer was washed with 1.0 M aqueous hydrochloric acid solution (50 mL)
  6. addition1.0 M aqueous sodium hydroxide solution (75 mL) was added
  7. extractionthe aqueous layer was extracted with ethyl acetate (100 mL)
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-e9c593998ed54bc7aacb9403519e2a55
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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