Chlorodifluoromethane → (E)-2-(fluoromethylene)-4-(p-fluorophenyl)butan-1-ol

HRID 1449847Notes

Reaction equation

HRID 1449847 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][CH2:20][C:21]([O:23]C(C)(C)C)=O)=[CH:14][CH:13]=1.ClC(OCC)=O.Cl[CH:35](F)[F:36]>C(O)(=O)C.O1CCCC1>[F:36]/[CH:35]=[C:20](\[CH2:19][CH2:18][C:15]1[CH:14]=[CH:13][C:12]([F:11])=[CH:17][CH:16]=1)/[CH2:21][OH:23]

Participants

7

Reactant 4

HCID 6372ChlorodifluoromethaneHCID 10928Ethyl chloroformateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 15342049t-Butyl 4-(p-fluorophenyl)butyrate

Product 1

HCID 10943450(E)-2-(fluoromethylene)-4-(p-fluorophenyl)butan-1-ol

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

Cool a tetrahydrofuran solution of sodium bis(trimethylsilyl)amide (545 kg, 2M, 877 mol) to -10° C. Slowly add, t-butyl 4-(p-fluorophenyl)butyrate (84.1 kg, 80% by weight in toluene, 353 mol). After 15 minutes, slowly add ethyl chloroformate (38.6 kg, 356 mol) at such a rate that the reaction temperature is maintained at or below -5° C. After 20 minutes, warm the reaction mixture to 40° C.-45° C. Seal the reaction vessel and add chlorodifluoromethane (38.15 kg, 445 mol) to the head space. After 1 hour, cool to 15° C.-20° C. and vent the reaction vessel. Add a solution of acetic acid (421 kg, 20% in water) and stir. After 30 minutes, separate the aqueous layer and evaporate the organic layer in vacuo to obtain a residue. Add toluene (45 kg) and evaporate in vacuo until the internal temperature of the reaction vessel is 55° C. to obtain the title compound as a toluene solution.

Workup

  1. additionSlowly add
  2. waitAfter 20 minutes
  3. temperaturewarm the reaction mixture to 40° C.-45° C
  4. customSeal the reaction vessel
  5. waitAfter 1 hour
  6. temperaturecool to 15° C.-20° C.
  7. waitAfter 30 minutes
  8. customseparate the aqueous layer
  9. customevaporate the organic layer in vacuo
  10. customto obtain a residue
  11. customAdd toluene (45 kg) and evaporate in vacuo until the internal temperature of the reaction vessel
  12. customis 55° C.

Sources & evidence

ORD record
ord-06213b8482964feb99bc7e4b6539b120
Source dataset
uspto-grants-1997_02
Patent number
US05599986

Reaction notes

Loading…