Diethyl Ether → Methyl 6,6-difluoro-5-methyl-5-hexenoate

HRID 917403Notes

Reaction equation

HRID 917403 reaction equation
Br[C:2](Br)([F:4])[F:3].CN(P(N(C)C)N(C)C)C.O=[C:17]([CH3:25])[CH2:18][CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22].C(OCC)C>O1CCCC1>[F:3][C:2]([F:4])=[C:17]([CH3:25])[CH2:18][CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 6382DibromodifluoromethaneHCID 15355Hexamethylphosphorous triamideHCID 84129Methyl 5-oxohexanoate

Product 1

HCID 23020142Methyl 6,6-difluoro-5-methyl-5-hexenoateYield 89.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Reaction was carried out under nitrogen atmosphere. To 650 ml of tetrahydrofuran, 80 g (0.38 mol) of dibromodifluoromethane was dissolved, followed by drop-wisely adding 121 g (0.74 mol) of tris(dimethylamino)phosphine at −10° C. After the end of the drop-wise addition, the reaction liquid was stirred at room temperature for 1 hour, followed by further drop-wisely adding 24.9 g (0.17 mol) of methyl 5-oxohexanoate dissolved in 250 ml of tetrahydrofuran, at −20° C. After the end of the drop-wise addition, the reaction liquid was stirred at room temperature overnight. To this mixture, diethyl ether was added, followed by washing with dilute hydrochloric acid, a saturated aqueous solution of sodium hydrogencarbonate and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentrating under reduced pressure. The residue was purified by silica gel column chromatography (diethyl ether:hexane=1:4) to obtain 27 g (yield: 88%) of methyl 6,6-difluoro-5-methyl-5-hexenoate.

Workup

  1. customReaction
  2. additionAfter the end of the drop-wise addition
  3. customthe reaction liquid
  4. additionAfter the end of the drop-wise addition
  5. customthe reaction liquid
  6. stirringwas stirred at room temperature overnight
  7. washby washing with dilute hydrochloric acid
  8. dry with materialby drying over anhydrous magnesium sulfate
  9. concentrationconcentrating under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (diethyl ether:hexane=1:4)

Sources & evidence

ORD record
ord-8e3be19019b1434bab3ba64a1507d8c1
Source dataset
uspto-grants-2007_09
Patent number
US07273878B2

Reaction notes

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