Heptane → (R)-tert-Butyl 2,2,4-trimethyl-4-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-yl)oxazolidine-3-carboxylate

HRID 2357099Notes

Reaction equation

HRID 2357099 reaction equation
COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:10])=CC=1.[CH3:23][C:24]1([CH3:62])[N:28]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@:27]([CH3:61])([C:36]([NH:38][NH:39][C:40](=O)[C:41]2[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])=[C:43]([C:56]([F:59])([F:58])[F:57])[CH:42]=2)=O)[CH2:26][O:25]1.C([O-])(O)=O.[Na+].CCCCCCC>C1(C)C=CC=CC=1>[CH3:23][C:24]1([CH3:62])[N:28]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C@@:27]([CH3:61])([C:36]2[S:10][C:40]([C:41]3[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])=[C:43]([C:56]([F:59])([F:58])[F:57])[CH:42]=3)=[N:39][N:38]=2)[CH2:26][O:25]1

Participants

6

Reactant 4

HCID 8900HeptaneHCID 87949Lawesson's reagentHCID 516892Sodium BicarbonateHCID 53349361HCID 53349361, compound

Product 1

HCID 59384428(R)-tert-Butyl 2,2,4-trimethyl-4-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-1,3,4-thiadiazol-2-yl)oxazolidine-3-carboxylateYield 75.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20.5 °C

Procedure

A 12 L, round bottom flask was inerted and charged with Lawesson's reagent (211.5 g, 0.52 mol, 1.2 equiv), a solution of (S)-tert-butyl 2,2,4-trimethyl-4-(2-(4-(octyloxy)-3-(trifluoromethyl)benzoyl)-hydrazinecarbonyl)oxazolidine-3-carboxylate (D8A) (250 g—based on theoretical output, 0.43 mol) in toluene (2.5 L), and the resulting slurry was heated to 80° C. and held for 3 hours. TLC indicated the reaction was complete. The mixture was cooled to 18-23° C., charged with saturated NaHCO3 solution (2 L), which was slightly exothermic. The aqueous was extracted twice with ethyl acetate (2 L, 1.5 L), the organic phases were combined, concentrated, dissolved in dichloromethane (500 mL), charged with silica-gel (500 g), concentrated to remove dichloromethane, and purified using a silica-gel (2.5 kg) column which was eluted with 5% ethyl acetate: 95% heptane to afford the title product (185 g, 74% yield, 95% AUC by HPLC) as a yellow color oil.

Workup

  1. extractionThe aqueous was extracted twice with ethyl acetate (2 L, 1.5 L)
  2. concentrationconcentrated
  3. dissolutiondissolved in dichloromethane (500 mL)
  4. additioncharged with silica-gel (500 g)
  5. concentrationconcentrated
  6. customto remove dichloromethane
  7. custompurified
  8. washwas eluted with 5% ethyl acetate

Sources & evidence

ORD record
ord-933497eeb29546d08273ba59cb2e9447
Source dataset
uspto-grants-2010_07
Patent number
US07759370B2

Reaction notes

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