Dimethylformamide → HCID 58573664, compound

HRID 932287Notes

Reaction equation

HRID 932287 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[CH:9]=[C:10]([C@H:14]([C@@:20]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)([NH:22][CH:23]([CH3:25])[CH3:24])[CH3:21])[CH2:15][CH2:16][C:17]([OH:19])=O)[CH:11]=[CH:12][CH:13]=1.CN(C=O)C>C1C=CC=CC=1>[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:14]2[C@:20]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)([CH3:21])[N:22]([CH:23]([CH3:24])[CH3:25])[C:17](=[O:19])[CH2:16][CH2:15]2)[CH:11]=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 58574019HCID 58574019, compound

Product 1

HCID 58573664HCID 58573664, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

Oxalyl chloride (˜0.38 M in benzene, 0.617 mL, 0.234 mmol) was added to a room temperature solution of (4R,5S)-4-(3-chlorophenyl)-5-(4-chlorophenyl)-5-(isopropylamino)hexanoic acid (Example 418, Step G, 84 mg, 0.213 mmol) in benzene (3 mL) followed by a drop of DMF. The reaction solution was stirred at room temperature for 25 minutes then heated to 80° C. After 3.5 hours the reaction was removed from heat and saturated aqueous sodium bicarbonate solution was added. The organic phase was diluted with ethyl acetate. The aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with brine, then dried with anhydrous magnesium sulfate and concentrated to afford a red-orange oil. The product was isolated by chromatography on silica (12 g RediSep Rf cartridge) eluting with 20-40% ethyl acetate gradient in hexane to afford the title compound as a pale yellow film. [α]D=+ 89.33° (T=24.0° C.; c=1, CHCl3)

Workup

  1. temperaturethen heated to 80° C
  2. customAfter 3.5 hours the reaction was removed
  3. temperaturefrom heat
  4. additionsaturated aqueous sodium bicarbonate solution was added
  5. additionThe organic phase was diluted with ethyl acetate
  6. extractionThe aqueous layer was extracted again with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried with anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. customto afford a red-orange oil
  11. customThe product was isolated by chromatography on silica (12 g RediSep Rf cartridge)
  12. washeluting with 20-40% ethyl acetate gradient in hexane

Sources & evidence

ORD record
ord-d06230f25aa84a9fac761f321c2bd036
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

Loading…