1-Cyclopentyl-2-propen-1-ol → 1-Cyclopentyl-3-[3-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]propan-1-one

HRID 858673Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[C:4]([F:12])[CH:3]=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+]>CN1C(=O)CCC1.[NH4+].[Cl-].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>[CH:13]1([C:18](=[O:21])[CH2:19][CH2:20][C:2]2[CH:7]=[CH:6][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[C:4]([F:12])[CH:3]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of 2-(4-bromo-2-fluorophenyl)propan-2-ol (5.8 g, 25.0 mmol) in anhydrous NMP (63 mL) was added 1-Cyclopentyl-2-propen-1-ol (3.15 g, 25.0 mmol), NaHCO3 (4.2 g, 50 mmol) and PdCl2(PPh3)2 (350 mg, 2 mol %). The mixture was heated to 140° C. for 4 hours before it was cooled down to room temperature. The reaction was diluted with aqueous NH4Cl, extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine, dried with Na2SO4 and evaporated to dryness. The mixture was purified by flash column chromatography (10–50% EtOAc in hexanes) to give the product (2.5 g, 36% yield). 1H NMR (300 MHz, CDCl3) δ: 1.56–1.82 (m, 8 H), 1.62 (s, 6 H), 2.74–2.78 (m, 2 H), 2.82–2.89 (m, 2 H), 6.84–6.88 (m, 1 H), 6.93–6.95 (m, 1 H), 7.40–7.44 (m, 1 H).

Workup

temperaturewas cooled down to room temperature
extractionextracted with EtOAc (3×50 mL)
washThe combined organic extracts were washed with brine
dry with materialdried with Na2SO4
customevaporated to dryness
customThe mixture was purified by flash column chromatography (10–50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-b4c97b47427a48b591b313982db3b2b3
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07148226B2

Reaction notes

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