Triethylamine → trans-2-(2-Cyclopropylethylamino)-cyclopentanecarboxylic acid ethyl ester

HRID 731289Notes

Reaction equation

HRID 731289 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][C@H:4]1[C:8]([O:10][CH2:11][CH3:12])=[O:9].C(N(CC)CC)C.[CH:20]1([CH2:23][CH:24]=O)[CH2:22][CH2:21]1.C([BH3-])#N.[Na+]>C(O)C>[CH2:11]([O:10][C:8]([C@@H:4]1[CH2:5][CH2:6][CH2:7][C@@H:3]1[NH:2][CH2:24][CH2:23][CH:20]1[CH2:22][CH2:21]1)=[O:9])[CH3:12].[CH2:11]([O:10][C:8]([C@@H:4]1[CH2:5][CH2:6][CH2:7][C@H:3]1[NH:2][CH2:24][CH2:23][CH:20]1[CH2:22][CH2:21]1)=[O:9])[CH3:12]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2725067Ethyl cis-2-amino-1-cyclopentane carboxylate hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 103078492-Cyclopropylacetaldehyde

Product 2

HCID 69061399trans-2-(2-Cyclopropylethylamino)-cyclopentanecarboxylic acid ethyl esterYield 90.5%HCID 69063495cis-2-(2-Cyclopropylethylamino)-cyclopentanecarboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of cis-ethyl 2-amino-1-cyclopentanecarboxylate hydrochloride (250.0 mg, 1.28 mmol) in ethanol (5 mL) was added triethylamine (0.2 mL, 1.42 mmol), cyclopropylacetaldehyde (288.0 mg, 1.92 mmol), and sodium cyanoborohydride (59.2 mg, 0.895 mmol) at 25° C. After stirring for 12 h, the mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The crude material was purified by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-50% ethyl acetate in hexanes) to afford cis-2-(2-cyclopropylethylamino)-cyclopentanecarboxylic acid ethyl ester as a yellowish oil (42.7 mg, 0.189, 15%) and trans-2-(2-cyclopropylethylamino)-cyclopentanecarboxylic acid ethyl ester as a yellowish oil (130.5 mg, 0.579 mmol, 45%). cis-2-(2-Cyclopropylethylamino)-cyclopentanecarboxylic acid ethyl ester: 1H NMR (400 MHz, CDCl3) δ 0.08-0.12 (2H, m), 0.45-0.49 (2H, m), 0.63-0.72 (1H, m), 1.29 (3H, t, J=7.0 Hz), 1.46-1.52 (2H, m), 1.58-1.77 (2H, m), 1.85-2.10 (4H, m), 2.73-2.87 (2H, m), 3.03 (1H, q, J=6.7 Hz), 3.36 (1H, q, J=7.3 Hz), 4.17 (2H, q, J=7.0 Hz). LC-MS (ESI) calcd for C13H23NO2 225.17, found 226.2 [M+H+]. trans-2-(2-Cyclopropylethylamino)-cyclopentanecarboxylic acid ethyl ester: 1H NMR (400 MHz, CDCl3) δ 0.12-0.16 (2H, m), 0.50-0.55 (2H, m), 0.65-0.72 (1H, m), 1.31 (3H, t, J=7.1 Hz), 1.53-1.59 (2H, m), 1.64-1.84 (2H, m), 1.89-2.13 (4H, m), 2.81-2.87 (1H, m), 2.95-3.01 (1H, m), 3.07 (1H, q, J=7.1 Hz), 3.44 (1H, q, J=7.2 Hz), 4.20 (2H, q, J=7.0 Hz). LC-MS (ESI) calcd for C13H23NO2 225.17, found 226.2 [M+H+].

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2ccdab956d3d458994740f7a4b899808
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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