Pyridine → cis-2-(3-Methylbutylamino)-cyclopentanecarboxylic acid ethyl ester

HRID 731281Notes

Reaction equation

HRID 731281 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH2:10][CH2:9][CH2:8][C:7]=1[NH:11][CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15])=[O:5])[CH3:2].B.N1C=CC=CC=1>C(O)(=O)C>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@@H:7]1[NH:11][CH2:12][CH2:13][CH:14]([CH3:15])[CH3:16])=[O:5])[CH3:2].[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[NH:11][CH2:12][CH2:13][CH:14]([CH3:15])[CH3:16])=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 1049PyridineHCID 6331BoraneHCID 57671248HCID 57671248, compound

Product 2

HCID 57671252cis-2-(3-Methylbutylamino)-cyclopentanecarboxylic acid ethyl esterYield 34%HCID 69061408trans-2-(3-Methylbutylamino)-cyclopentanecarboxylic acid ethyl esterYield 17%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 2-(3-methylbutylamino)-cyclopent-1-enecarboxylic acid ethyl ester (6.84 g, 30.4 mmol) in acetic acid (100 mL) was added a 8.0 M solution of borane in pyridine (4.6 mL, 36.8 mmol) at 25° C. After stirring for 15 min, the reaction mixture was concentrated in vacuo. The crude material was triturated with 1.0 M aqueous hydrochloric acid solution (25 mL) and stirred for 0.5 h (until the gas evolution ceased). The mixture was extracted with ethyl acetate (3×50 mL) and the combined organic layers were dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude material was purified by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-10% methanol in dichloromethane) to afford cis-2-(3-methylbutylamino)-cyclopentanecarboxylic acid ethyl ester (2.37 g, 10.4 mmol, 34%) as a colorless oil and trans-2-(3-methylbutylamino)-cyclopentanecarboxylic acid ethyl ester (1.18 g, 5.2 mmol, 17%) as a white solid. cis-2-(3-Methylbutylamino)-cyclopentanecarboxylic acid ethyl ester: 1H NMR (400 MHz, CDCl3) δ 0.90 (6H, d, J=6.3 Hz), 1.26 (3H, t, J=7.0 Hz), 1.34-1.46 (3H, m), 1.57-1.74 (4H, m), 1.81-1.90 (1H, m), 1.94-2.04 (2H, m), 2.53 (1H, q, J=8.1 Hz), 2.59 (2H, t, J=7.5 Hz), 3.27 (1H, q, J=7.6 Hz), 4.11-4.17 (2H, m). trans-2-(3-Methylbutylamino)-cyclopentanecarboxylic acid ethyl ester: 1H NMR (400 MHz, CDCl3) δ: 0.92 (6H, d, J=6.8 Hz), 1.28 (3H, t, J=7.3 Hz), 1.41-1.47 (2H, m), 1.51-1.90 (5H, m), 2.00-2.09 (3H, m), 2.62-2.74 (3H, m), 3.38 (1H, q, J=7.2 Hz), 4.16 (2H, q, J=7.0 Hz). LC-MS (ESI) calcd for C13H25NO2 227.19, found 228.3 [M+H+].

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customThe crude material was triturated with 1.0 M aqueous hydrochloric acid solution (25 mL)
  3. stirringstirred for 0.5 h (until the gas evolution
  4. extractionThe mixture was extracted with ethyl acetate (3×50 mL)
  5. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-ad6970a4fed04b51ba30166834e1a858
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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