Cesium carbonate → 4-Acetyl-6-chloro-3-ethoxy-2-pyrrolidin-1-ylbenzonitrile

HRID 1499920Notes

Reaction equation

[C:1]([C:4]1[CH:11]=[C:10]([Cl:12])[C:7]([C:8]#[N:9])=[C:6](I)[C:5]=1[O:14][CH2:15][CH3:16])(=[O:3])[CH3:2].[NH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[C:1]([C:4]1[CH:11]=[C:10]([Cl:12])[C:7]([C:8]#[N:9])=[C:6]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:5]=1[O:14][CH2:15][CH3:16])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

The 4-acetyl-6-chloro-3-ethoxy-2-iodobenzonitrile (0.20 g, 0.57 mmol) was combined with pyrrolidine (0.052 mL, 0.63 mmol) in N,N-dimethylformamide (2.0 mL) with cesium carbonate (0.19 g, 0.57 mmol) and heated to 120° C. in a sealed tube. After heating for 18 hrs the reaction was allowed to cool, taken up in ethyl acetate, washed with water, brine, dried over magnesium sulfate and concentrated to give the crude product as a dark oil. The product was purified by FCC on silica gel eluting with hexane:ethyl acetate gradient to give 4-acetyl-6-chloro-3-ethoxy-2-pyrrolidin-1-ylbenzonitrile as an oil (0.045 g, 27%). LCMS calculated for C15H18ClN2O2(M+H)+: m/z=293.1; found 293.1.

Workup

temperatureAfter heating for 18 hrs the reaction
temperatureto cool
washwashed with water, brine
dry with materialdried over magnesium sulfate
concentrationconcentrated
customto give the crude product as a dark oil
customThe product was purified by FCC on silica gel eluting with hexane

Sources & evidence

ORD record: ord-8ac6537717884de587880f096570abea
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199982B2

Reaction notes

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