1-Cyclopentyl-2-propen-1-ol → 3-(3-Chloro-5-ethyl-4-methoxy-phenyl)-1-cyclopentyl-propan-1-one

HRID 1453225Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH2:11][CH3:12])[C:5]([O:9][CH3:10])=[C:6]([Cl:8])[CH:7]=1.[CH:13]1([CH:18]([OH:21])[CH:19]=[CH2:20])[CH2:17][CH2:16][CH2:15][CH2:14]1.C(=O)(O)[O-].[Na+]>CN1CCCC1=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:8][C:6]1[CH:7]=[C:2]([CH2:20][CH2:19][C:18]([CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:21])[CH:3]=[C:4]([CH2:11][CH3:12])[C:5]=1[O:9][CH3:10]

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of 5-bromo-1-chloro-3-ethyl-2-methoxy-benzene (2 g, 8 mmol), 1-Cyclopentyl-2-propen-1-ol (1.31 g, 10.4 mmol), dichlorobis(triphenylphosphine)palladium (II) (110 mg, 0.16 mmol), and sodium bicarbonate (0.81 g, 9.6 mmol) in N-methylpyrrolidinone (15 mL) was heated to 140° C. under N2 for 5 h. The reaction mixture was partitioned between 1N HCl and EtOAc. The organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated to a black oil. The oil was purified by flash column chromatography (0% to 10% EtOAc in hexanes) to give the desired product (1.9 g, 82%). 1H NMR (400 MHz, CDCl3): δ 1.20 (t, J=7.6 Hz, 3H), 1.53-1.81 (m, 8H), 2.65 (q, J=7.6 Hz, 2H), 2.74 (m, 2H), 2.79-2.87 (m, 3H), 3.81 (s, 3H), 6.90 (s, 1H), 7.03 (m, 1H).

Workup

customThe reaction mixture was partitioned between 1N HCl and EtOAc
washThe organic layer was washed with saturated NaHCO3, brine
dry with materialdried over Na2SO4
concentrationconcentrated to a black oil
customThe oil was purified by flash column chromatography (0% to 10% EtOAc in hexanes)

Sources & evidence

ORD record: ord-b34605c1fa89480195b27b087f996160
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07473790B2

Reaction notes

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