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

HRID 1873304Notes

Reaction equation

HRID 1873304 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 to a soln. of 20.0 g (0.12 mol) of 7,8-difluorochroman in 400 ml of THF at −70° C. After 3 h at this temperature, 14.4 ml (0.13 mol) of trimethyl borate are added dropwise, and the batch is warmed to RT. 30 ml of dilute acetic acid (about 30%) are added, and 30 ml of aqueous hydrogen peroxide solution (35%) are carefully added to the batch. When the addition is complete, the mixture is stirred at RT for 17 h. Water is added, and the batch is acidified using 2 N hydrochloric acid. 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 evaporated to dryness. The crude product is purified by column chromatography (SiO2, n-heptane: MTBE=2:1).

Workup

  1. customat −70° C
  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. customevaporated to dryness
  7. customThe crude product is purified by column chromatography (SiO2, n-heptane: MTBE=2:1)

Sources & evidence

ORD record
ord-f29fcaece21647d98b814a1eb29ba48a
Source dataset
uspto-grants-2012_11
Patent number
US08303844B2

Reaction notes

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