Triethylborane → 1-Cyclopentyl-3-(5-ethoxy-2-ethyl-pyridin-4-yl)-propan-1-one

HRID 1438360Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][C:10]([CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[O:11])[C:5]([O:17][CH2:18][CH3:19])=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:26](B(CC)CC)[CH3:27]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:12]1([C:10](=[O:11])[CH2:9][CH2:8][C:6]2[C:5]([O:17][CH2:18][CH3:19])=[CH:4][N:3]=[C:2]([CH2:26][CH3:27])[CH:7]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

Conditions

Temperature: 150 °C

Procedure

A solution of 3-(2-chloro-5-ethoxy-pyridin-4-yl)-1-cyclopentyl-propan-1-one (1.2 g, 4.3 mmol) dissolved in DMF (10 mL) was treated with potassium carbonate (0.88 g, 6.4 mmol), tetrakis(triphenylphosphine)palladium (0.12 g, 0.11 mmol), and triethylborane (4.5 mL, 4.5 mmol). The reaction was heated to 150° C. for 2 hours. The reaction was quenched with 1 N HCl and then made basic with 2 N NaOH. The mixture was extracted with ether and the organic layers were dried over MgSO4 and concentrated. Purification by silica gel chromatography (0% to 60% EtOAc in hexanes) gave the product (0.8 g, 68%). 1H NMR (300 MHz, CDCl3): δ 1.26 (t, J=7.6 Hz, 3H), 1.42 (t, J=6.9 Hz, 3H), 1.55-1.87 (m, 8H), 2.73 (m, 4H), 2.86 (m, 3H), 4.11 (q, J=6.9 Hz, 2H), 6.93 (s, 1H), 8.06 (s, 1H).

Workup

customThe reaction was quenched with 1 N HCl
extractionThe mixture was extracted with ether
dry with materialthe organic layers were dried over MgSO4
concentrationconcentrated
customPurification by silica gel chromatography (0% to 60% EtOAc in hexanes)

Sources & evidence

ORD record: ord-6bb3ddd35cf547199ecd9ef958cdc7c0
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07622605B2

Reaction notes

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