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

HRID 731285Notes

Reaction equation

HRID 731285 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][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:5])[CH3:2].B.N1C=CC=CC=1.C(OC([C@@H]1CCC[C@H]1NCCC(C)(C)C)=O)C>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][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6331BoraneHCID 576712592-(3,3-Dimethylbutylamino)-cyclopent-1-enecarboxylic acid ethyl esterHCID 69061522trans-2-(3,3-Dimethylbutylamino)-cyclopentanecarboxylic acid ethyl ester

Product 1

HCID 57671253cis-2-(3,3-Dimethylbutylamino)-cyclopentanecarboxylic acid ethyl esterYield 7.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 2-(3,3-dimethylbutylamino)-cyclopent-1-enecarboxylic acid ethyl ester (5.59 g, 23.4 mmol) in acetic acid (70 mL) was added a 8.0 M solution of borane in pyridine (3.2 mL, 25.6 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-(3,3-dimethylbutylamino)-cyclopentanecarboxylic acid ethyl ester as a yellowish oil (0.40 g, 1.7 mmol, 7%) and trans-2-(3,3-dimethylbutylamino)-cyclopentanecarboxylic acid ethyl ester and an off-white solid (2.37 g, 9.8 mmol, 42%). cis-2-(3,3-Dimethylbutylamino)-cyclopentanecarboxylic acid ethyl ester: 1H NMR (400 MHz, CDCl3) δ 0.91 (9H, s), 1.28 (3H, t, J=7.0 Hz), 1.35-1.50 (2H, m), 1.56-1.73 (2H, m), 1.80-2.03 (4H, m), 2.60-2.75 (2H, m), 2.98-3.02 (1H, m), 3.35 (1H, q, J=7.4 Hz), 4.15 (2H, q, J=6.9 Hz), 6.38 (1H, s). trans-2-(3,3-Dimethylbutylamino)-cyclopentanecarboxylic acid ethyl ester: 1H NMR (400 MHz, CDCl3) δ 0.94 (9H, s), 1.29 (3H, t, J=7.0 Hz), 1.66-2.01 (6H, m), 2.11-2.27 (2H, m), 2.86 (2H, t, J=8.6 Hz), 3.10 (1H, q, J=7.8 Hz), 3.68 (1H, q, J=7.0 Hz), 4.18 (2H, q, J=7.0 Hz). LC-MS (ESI) calcd for C14H27NO2 241.20, found 242.4 [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-0e3969265ac04d94858694f4bc04a13c
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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