HCID 69315922, compound → HCID 69318208, compound

HRID 2115159Notes

Reaction equation

HRID 2115159 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([F:17])[CH:16]=1)[O:13][C:12](=[O:18])[CH2:11][CH2:10]2.[O:19]1[CH2:23][CH2:22][O:21][CH:20]1[CH:24]1[CH2:29][CH2:28][CH:27]([CH:30]2[CH2:35][CH2:34][C:33](=[O:36])[CH2:32][CH2:31]2)[CH2:26][CH2:25]1>C1COCC1.[Br-].[Zn+2].[Br-]>[F:17][C:15]1[CH:16]=[C:7]([C:33]2([OH:36])[CH2:34][CH2:35][CH:30]([CH:27]3[CH2:26][CH2:25][CH:24]([CH:20]4[O:21][CH2:22][CH2:23][O:19]4)[CH2:29][CH2:28]3)[CH2:31][CH2:32]2)[CH:8]=[C:9]2[C:14]=1[O:13][C:12](=[O:18])[CH2:11][CH2:10]2

Participants

6

Reactant 3

HCID 69315922HCID 69315922, compoundHCID 69318670HCID 69318670, compoundHCID 178418339Butyllithium

Product 1

HCID 69318208HCID 69318208, compoundYield 54.9%

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-100 °C

Procedure

Butyllithium (1.6 ml, 1.5 M) was added dropwise to a solution of 6-bromo-8-fluoro-3,4-dihydrocoumarin (4.8 g) in THF (50 ml) as cooled at −100° C. in an argon gas stream. After completion of the dropwise addition, the temperature of the reaction mixture was raised to −78° C., and a solution of zinc bromide (5 g) in THF (100 ml) was added dropwise thereto. After completion of the dropwise addition, the temperature of the reaction mixture was raised to −30° C., and a solution of 4-(4-(1,3-dioxolan-2-yl)cyclohexyl)cyclohexanone (5.0 g) in THF (50 ml) was added dropwise thereto. After completion of the dropwise addition, the temperature of the reaction mixture was raised to room temperature, followed by stirring for 18 hours. The reaction mixture was added in ice water, extracted with toluene, washed with water, and then dried over anhydrous magnesium sulfate. The solution was concentrated in vacuo and then subjected to isolation and purification by silica gel column chromatography, thereby obtaining a colorless crystal of 1-(8-fluoro-3,4-dihydrocoumarin-6-yl)-4-(4-(1,3-dioxolan-2-yl)cyclohexyl)cyclohexanol (4.5 g).

Workup

  1. additionAfter completion of the dropwise addition
  2. temperaturethe temperature of the reaction mixture was raised to −78° C.
  3. additionAfter completion of the dropwise addition
  4. temperaturethe temperature of the reaction mixture was raised to −30° C.
  5. additionAfter completion of the dropwise addition
  6. temperaturethe temperature of the reaction mixture was raised to room temperature
  7. extractionextracted with toluene
  8. washwashed with water
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationThe solution was concentrated in vacuo
  11. customsubjected to isolation and purification by silica gel column chromatography

Sources & evidence

ORD record
ord-c01b490db6ff4298b3a388b36dbbac18
Source dataset
uspto-grants-2008_10
Patent number
US07435455B2

Reaction notes

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