Hydrochloric Acid → HCID 18325394, compound

HRID 1979145Notes

Reaction equation

HRID 1979145 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26](=[O:32])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[CH:22][CH:21]=2)=[CH:16][CH:15]=1.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:43])(=O)=O)=CC=1.Cl>O1CCCC1.CO>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26](=[O:32])[CH:27]([F:43])[CH2:28][C:29]([OH:31])=[O:30])=[CH:22][CH:21]=2)=[CH:18][CH:19]=1

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 7912DiisopropylamineHCID 588007N-FluorobenzenesulfonimideHCID 14116665HCID 14116665, compoundHCID 178418339Butyllithium

Product 1

HCID 18325394HCID 18325394, compoundYield 9.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of diisopropylamine (0.295 mL, 0.0021 mol) in anhydrous tetrahydrofuran (10 mL) at room temperature under nitrogen was added in portions a 2.1 M solution of n-butyl lithium in hexanes (1.0 mL, 0.0021 mol), and the mixture cooled to −78° C. To the solution was added a solution of 4-(4′-chloro-biphenyl-4-yl)-4-oxo-butyric acid (0.288 g, 0.000997 mol) in THF (10 mL), and the mixture stirred for 1 hour. To the yellow solution was added dropwise a solution of N-fluorodibenzenesulfonamide (NFSI, 0.346 g, 0.00110 mol) in THF (10 mL), and the mixture stirred for 2 hours at −78° C. The mixture was allowed to warm to room temperature and stirred for 16 hours. The reaction was quenched with 1 M hydrochloric acid (1.1 mL, 0.0011 mol HCl), and the mixture was rotary evaporated to dryness. The residue was passed through a column of silica gel, eluting with dichloromethane-methanol (10:1 then 9:1) to give a gum. The gum was dissolved in methanol and acidified with additional 1 M hydrochloric acid (3.4 mL, 0.0034 mol HCl). The volatiles were rotary evaporated, and the resulting suspension was filtered. The filter cake was purified by chromatography on silica gel, eluting with dichloromethane-methanol (14:1) to give 0.030 g of (±)-4-(4′-chloro-biphenyl-4-yl)-3-fluoro-4-oxo-butyric acid as a white solid; mp 170-173° C.

Workup

  1. stirringthe mixture stirred for 2 hours at −78° C
  2. temperatureto warm to room temperature
  3. stirringstirred for 16 hours
  4. customthe mixture was rotary evaporated to dryness
  5. washeluting with dichloromethane-methanol (10:1
  6. custom9:1) to give a gum
  7. filtrationthe resulting suspension was filtered
  8. customThe filter cake was purified by chromatography on silica gel
  9. washeluting with dichloromethane-methanol (14:1)

Sources & evidence

ORD record
ord-497a12fca83745fab686ba05df45aa9e
Source dataset
uspto-grants-2001_05
Patent number
US06239288B1

Reaction notes

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