Ammonium Chloride → 8-(4-Fluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol

HRID 2306775Notes

Reaction equation

[CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=[O:10])[CH2:6][CH2:5]2)[O:3][CH2:2]1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([Mg]Br)=[CH:15][CH:14]=1.[NH4+].[Cl-]>C1COCC1>[CH2:2]1[O:3][C:4]2([CH2:5][CH2:6][C:7]([C:16]3[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=3)([OH:10])[CH2:8][CH2:9]2)[O:11][CH2:1]1

Participants

Conditions

Temperature: -78 °C

Procedure

1,4-Cyclohexanedione mono-ethylene ketal (10.1 g, 64.7 mmol) was dissolved in anhydrous THF (100 mL), and the solution was cooled to −78° C. 4-Fluorophenylmagnesium bromide (78 mL of a 1.0 M solution in THF, 78 mmol) was added slowly over 10 minutes. After 20 minutes, saturated NH4Cl (10 mL) was added and the mixture allowed to warm to room temperature. The mixture was partitioned between CHCl3 and saturated NH4Cl. The organic layer was dried (Na2SO4), filtered through CELITE, and concentrated under reduced pressure. Purification by flash chromatography (silica gel, 1:9 to 3:7 EtOAc: hexanes, loaded in a minimum of CH2Cl2) gave 4-(4-fluoro-phenyl)-4-hydroxy-cyclohexanone ethylene ketal (10.9 g, 67%); 1H NMR (300 MHz, CDCl3) δ 7.5 (dd, J=8, 8 Hz, 2H), 7.05 (dd, J=8, 8 Hz, 2H), 4.00-3.91 (m, 5H), 2.25-2.08 (m, 4H), 1.85 (d, J=8 Hz, 2H), 1.65 (d, J=8 Hz, 2H).

Workup

temperatureto warm to room temperature
customThe mixture was partitioned between CHCl3 and saturated NH4Cl
dry with materialThe organic layer was dried (Na2SO4)
filtrationfiltered through CELITE
concentrationconcentrated under reduced pressure
customPurification by flash chromatography (silica gel, 1:9 to 3:7 EtOAc

Sources & evidence

ORD record: ord-e4d2a49ca896421b8b93057778e3cfd1
Source dataset: uspto-grants-2004_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06828341B2

Reaction notes

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