3-Bromoanisole → HCID 22397834, compound

HRID 2085453Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][CH:7]=1.[Li]CCCC.[CH2:15]([N:22]1[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1>[CH2:15]([N:22]1[CH2:27][CH2:26][C:25]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[CH:3]=2)([OH:28])[CH2:24][CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 3-bromoanisole (20.9 mL, 0.16 mmol) in THF (150 mL) at −78° C. under a nitrogen atmosphere was added n-BuLi (66 mL, 0.16 mmol, 2.5M in hexanes) over 10 min. The resulting slurry was stirred at −78° C. for 1 hour. To the mixture was added a solution an N-benzyl-4-piperidinone (27.8 mL, 0.15 mmol) in THF (30 mL). The reaction was stirred at −78° C. for 2 hours and at room temperature for 10 hours. The mixture was poured slowly over ice-water (100 mL) and the aqueous layer was washed with EtOAc (3×50 mL). The combined organic extracts were dried (MgSO4) and concentrated. The crude residue was purified by flash chromatography with hexanes/EtOAc (3:1) to afford 42.2 g of the alcohol (95% yield). 1HNMR (400 MHz, CDCl3) δ 7.35-7.22 (comp, 6H), 7.07-7.04 (comp, 2H), 6.80-6.77 (m, 1H), 3.80 (s, 1H), 3.58 (s, 1H), 2.79 (d, 2H), 2.48 (t, 2H), 2.19-2.13 (comp, 2H), 1.72 (dd, 2H), 1.58 (s, 1H); MS (M+1) 298.3.

Workup

stirringThe reaction was stirred at −78° C. for 2 hours and at room temperature for 10 hours
washthe aqueous layer was washed with EtOAc (3×50 mL)
dry with materialThe combined organic extracts were dried (MgSO4)
concentrationconcentrated
customThe crude residue was purified by flash chromatography with hexanes/EtOAc (3:1)

Sources & evidence

ORD record: ord-16d24142310443108d517c057d9371ab
Source dataset: uspto-grants-2004_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06720336B2

Reaction notes

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