Bromide ion → HCID 178447107, compound

HRID 579589Notes

Reaction equation

HRID 579589 reaction equation
CON(C)[C:4]([C@H:6]1[CH2:11][CH2:10][C@@H:9]([C:12]2([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[O:16][CH2:15][CH2:14][O:13]2)[CH2:8][CH2:7]1)=[O:5].[Br-].O.Cl>O1CCCC1>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([C:12]2([C@@H:9]3[CH2:8][CH2:7][C@H:6]([C:4](=[O:5])[CH2:8][CH2:7][CH:6]=[CH2:4])[CH2:11][CH2:10]3)[O:13][CH2:14][CH2:15][O:16]2)=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 259Bromide ionHCID 313Hydrochloric AcidHCID 962WaterHCID 178502716HCID 178502716, compound

Product 1

HCID 178447107HCID 178447107, compoundYield 168.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

While under a nitrogen atmosphere, a solution of cis-4-[2-(4-chlorophenyl)-[1,3]-dioxolan-2-yl]-cyclohexanecarboxylic acid, methoxy-methyl amide (1.36 g, 3.85 mmol), in tetrahydrofuran (10 mL) was cooled to 0° C. and treated with 4-butenylmagnesiun bromide (0.5 M in THF, 19.24 mL, 9.62 mmol) in a dropwise manner. The solution was stirred for 1 hour at 0° C. then allowed to warm to room temperature overnight. The resulting solution was poured into water, acidified to pH 3-4 with 1 N hydrochloric acid, and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 0-25% ethyl acetate in heptane) gave cis-1-{4-[2-(4-chlorophenyl)-[1,3]-dioxolan-2-yl]-cyclohexyl}pent-4-en-1-one as a colorless oil (1.13 g, 84%); 1H NMR (CDCl3, 300 MHz) δ 7.31 (d, J=7.5 Hz, 2H), 7.27 (d, J=7.5 Hz, 2H), 5.78 (m, 1H), 4.96 (m, 2H), 3.94 (m, 2H), 3.68 (m, 2H), 2.50 (m, 3H), 2.30 (m, 2H), 2.15 (dd, J=13, 3 Hz, 2H), 1.76 (tt, J=11, 3 Hz, 1H), 1.36-1.56 (m, 4H) and 1.25 (td, J=13, 3 Hz, 2H); MS (+CI): m/z for C20H25ClO3: expected 348.2. found 349.2 (M+H)+.

Workup

  1. temperatureto warm to room temperature overnight
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic phase was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (silica gel, 0-25% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-34f3b37490fd4fc3b67f825c1e752b66
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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