Hydrochloric Acid → 7,8-Difluorochroman-6-ol

HRID 2244829Notes

Reaction equation

HRID 2244829 reaction equation
[Li]CCCC.[F:6][C:7]1[C:16]([F:17])=[C:15]2[C:10]([CH2:11][CH2:12][CH2:13][O:14]2)=[CH:9][CH:8]=1.B(OC)(OC)[O:19]C.OO.Cl>C1COCC1.O.C(O)(=O)C>[F:6][C:7]1[C:16]([F:17])=[C:15]2[C:10]([CH2:11][CH2:12][CH2:13][O:14]2)=[CH:9][C:8]=1[OH:19]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 8470Trimethyl borateHCID 591673237,8-DifluorochromanHCID 178418339Butyllithium

Product 1

HCID 592152417,8-Difluorochroman-6-ol

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

81.2 ml (0.13 mol) of n-BuLi (15% soln. in hexane) are added at −70° C. to a soln. of 20.0 g (0.12 mol) of 7,8-difluorochroman in 400 ml of THF. After 3 h at this temperature, 14.4 ml (0.13 mol) of trimethyl borate are added dropwise, and the batch is warmed to room temperature. 30 ml of dilute acetic acid (about 30%) are added, and 30 ml of aq. hydrogen peroxide soln. (35%) are carefully added to the batch. When the addition is complete, the mixture is stirred at 20° C. for 17 h. Water is added, and the batch is acidified using HCl. The solution is extracted a number of times with MTBE, and the combined organic phases are washed successively with water, sat. sodium chloride soln. and ammonium iron(II) sulfate soln. The solution is dried using sodium sulfate and concentrated to dryness. The crude product is purified by column chromatography (SiO2, n-heptane:MTBE=2:1).

Workup

  1. addition(35%) are carefully added to the batch
  2. additionWhen the addition
  3. extractionThe solution is extracted a number of times with MTBE
  4. washthe combined organic phases are washed successively with water, sat. sodium chloride soln
  5. customThe solution is dried
  6. concentrationconcentrated to dryness
  7. customThe crude product is purified by column chromatography (SiO2, n-heptane:MTBE=2:1)

Sources & evidence

ORD record
ord-808ffefdfee94112b52765574e028683
Source dataset
uspto-grants-2010_03
Patent number
US07678929B2

Reaction notes

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