2-CYCLOPENTYLACETAMIDE synthesis

Yield: 98%

Reaction Conditions:

Stage #1:2-cyclopentylacetic acid with Carbonyldiimidazole in dichloromethane at 22; for 1 h;Inert atmosphere;
Stage #2: with ammonium hydroxide in dichloromethane;water at 0 - 20;

Steps:

Preparation of 2-cyclopentylacetamide (S1)
A flame-dried flask with stir bar was charged with cyclopentylacetic acid (2.56 g, 20.0 mmol, 1.0 equiv) and fitted with a rubber septum. The flask was evacuated and backfilled with N₂. ACS grade CH₂Cl₂ (66 mL, 0.3 M) was added via syringe. Carbonyl diimidazole (CDI, 4.06 g, 25.0 mmol, 1.25 equiv) was then added by briefly removing the septum and adding the solid as asingle portion. The reaction was left to stir at 22 °C for 1 h. After 1 h, the reaction flask wascooled at 0 °C in an ice water bath and aqueous NH₄OH (30%) (9.4 mL, 72.4 mmol, 3.6 equiv)) was added. Following NH₄OH addition, the reaction was allowed to slowly warm to room temperature by not removing the ice bath and stirred overnight. After stirring overnight, the biphasic suspension was transferred to a separatory funnel anddiluted with saturated aqueous NaHCO₃ (ca. amount of CH₂Cl₂). The reaction flask was rinsed with an additional 5 mL CH₂Cl₂ to ensure quantitative transfer. The organic phase was removedand the aqueous was extracted once more with CH₂Cl2. The combined organic phases were washed with 1 M HCl, dried over Na₂SO₄, filtered, and concentrated under reduced pressure. Typically, the crude material did not require further chromatographic purification. The product was obtained as a white solid (2.49 g, 98% yield) without chromatographic purification. ¹H NMR (400 MHz, CDCl₃) δ 5.85 (br s, 1H), 5.53 (br s, 1H), 2.24-2.15 (m, 3H), 1.87-1.82 (m,2H), 1.64-1.50 (m, 4H), 1.19-1.11 (m, 2H). ¹³C NMR (126 MHz, CDCl₃) δ 175.7, 42.1, 36.9, 32.5, 24.9. IR (neat) ν 3346 (br m), 3168 (br m), 2951 (m), 2867 (m), 1661 (s), 1629 (s), 1412 (s), 1353 (m), 1308 (m), 1250 (m), 1156 (m), 952 (w), 882 (w), 809 (w), 672 (s) cm^-1. TLC R_f = 0.19 in 1:1 CH₂Cl₂:EtOAc. HRMS (ESI) m/z: [M + H]⁺ Calcd for C₇H₁₃NO 128.1070; Found 128.1068.

References:

Shehata, Mina F.;Short, Melanie A.;Sanders, Matthew A.;Roizen, Jennifer L. [Tetrahedron,2019,vol. 75,# 24,p. 3186 - 3194] Location in patent:supporting information