Sodium Chloride → HCID 59305344, compound

HRID 2241003Notes

Reaction equation

HRID 2241003 reaction equation
[F:1][CH:2]([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:25])[C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([C:20]#[C:21][CH2:22][CH2:23]O)[CH:14]=2)=[O:12])=[CH:6][CH:5]=1.CN(S(F)(F)[F:31])C.C(=O)(O)[O-].[Na+].[Cl-].[Na+]>ClCCl>[F:1][CH:2]([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:25])[C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([C:20]#[C:21][CH2:22][CH2:23][F:31])[CH:14]=2)=[O:12])=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 123203Sulfur, trifluoro(N-methylmethanaminato)-HCID 516892Sodium BicarbonateHCID 59305318HCID 59305318, compound

Product 1

HCID 59305344HCID 59305344, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

In a 100 mL round bottom dissolve 1-(4-Difluoromethoxy-phenyl)-2-[4-fluoro-3-(4-hydroxy-but-1-ynyl)-phenyl]-ethane-1,2-dione (0.670 g, 1.85 mmol) was dissolved in dichloromethane (40 mL) and chilled to −78° C. Add (Dimethylamino)sulfur trifluoride (MeDAST; 2.99 g, 22.4 mmol) was introduced via syringe injection. After 30 minutes dry-ice bath was removed. After 2 hours at ambient temperature the crude reaction was carefully poured into a 500 mL beaker containing 200 cc ice-chips and sodium bicarbonate. An attempted diethyl ether extraction with diethyl ether resulted in emulsion. Sodium chloride was added to break emulsion. Organic layer was concentrated to a residue, and loaded directly on top of an 80 gm chromatography column. Purification [YAMAZEN W-Prep 2XY using automatic gradient elution: 3% EtOAc/hexanes (hold 4 min) to 24% EtOAc (in 12 min), hold 8 minutes] afforded oil that begins to solidify as a wax 360 mg (53%).

Workup

  1. customAfter 30 minutes dry-ice bath was removed
  2. customAfter 2 hours at ambient temperature the crude reaction
  3. additionwas carefully poured into a 500 mL beaker
  4. extractionAn attempted diethyl ether extraction with diethyl ether
  5. customresulted in emulsion
  6. concentrationOrganic layer was concentrated to a residue
  7. customPurification [YAMAZEN W-Prep 2XY using automatic gradient elution: 3% EtOAc/hexanes (hold 4 min) to 24% EtOAc (in 12 min), hold 8 minutes]
  8. customafforded oil

Sources & evidence

ORD record
ord-dacd9c3cbe364cf8b96398fe31771f99
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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