Cyclopentylamine → Ethyl 4-cyano-3-(cyclopentylamino)benzoate

HRID 906143Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[C:13]#[N:14])[C:5]([O:7][CH2:8][CH3:9])=[O:6].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:63]1([NH2:68])[CH2:67][CH2:66][CH2:65][CH2:64]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:13]([C:12]1[CH:11]=[CH:10][C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:3][C:2]=1[NH:68][CH:63]1[CH2:67][CH2:66][CH2:65][CH2:64]1)#[N:14]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of ethyl 3-bromo-4-cyanobenzoate (500 mg, 1.97 mmol), XANTPHOS (228 mg, 0.39 mmol), cesium carbonate (1.282 g, 3.94 mmol), cyclopentylamine (233 mg, 2.75 mmol), and tris(dibenzylideneacetone)dipalladium (180 mg, 0.20 mmol) in dioxane (5 mL) was stirred at 100° C. for 17 h. The reaction mixture was partitioned between ethyl acetate (100 mL) and water (50 mL), the organic layer washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated. Column chromatography on silica (hexanes:ethyl acetate 9:1) afforded ethyl 4-cyano-3-(cyclopentylamino)benzoate (366 mg, 72% yield) as a brown oil. 1H NMR (400 MHz, CDCl3): 7.43 (m, 2H), 7.35 (m, 1H), 7.27 (m, 1H), 4.62 (d, 1H), 4.38 (q, 2H), 3.93 (m, 1H), 2.10 (m, 2H), 1.78 (m, 2H), 1.67 (m, 2H), 1.53 (m, 2H), 1.39 (t, 3H). MS (EI) for C15H18N2O2: 259 (MH+).

Workup

customThe reaction mixture was partitioned between ethyl acetate (100 mL) and water (50 mL)
washthe organic layer washed with brine (50 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-b3eb8b5c8fab49148cfdb80524cfa6a5
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012956B2

Reaction notes

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