Acetic Acid → HCID 58062837, compound

HRID 1951932Notes

Reaction equation

HRID 1951932 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]=[C:12]([C:14]3[O:18][N:17]=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[C:15]=3[C:25]([F:28])([F:27])[F:26])[O:11][N:10]=2)=[CH:5][CH:4]=1.[NH:29]1[CH2:32][CH:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:30]1.C(O)(=O)C.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[N:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[C:16]1[C:15]([C:25]([F:27])([F:26])[F:28])=[C:14]([C:12]2[O:11][N:10]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([CH2:2][N:29]4[CH2:30][CH:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:32]4)=[CH:8][CH:7]=3)[N:13]=2)[O:18][N:17]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 21828700tert-Butyl azetidine-3-carboxylateHCID 58062842HCID 58062842, compound

Product 1

HCID 58062837HCID 58062837, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(4-(bromomethyl)phenyl)-5-(3-(pyridin-2-yl)-4-(trifluoromethyl)-isoxazol-5-yl)-1,2,4-oxadiazole (2.52 g, 5.59 mmol) and tert-butyl azetidine-3-carboxylate, acetic acid (1.82 g, 8.39 mmol) in N,N-dimethylformamide (40 mL) cooled with an ice-water bath was added triethylamine (2.34 mL, 16.8 mmol) drop-wise. The reaction mixture was stirred for 30 minutes, diluted with ethyl acetate (350 mL), washed with a 10% aqueous solution of lithium chloride (2×100 mL), washed with water (100 mL), washed with brine (100 mL), and dried over anhydrous sodium sulfate. Concentration gave a crude product which was triturated with methanol. The resulting solid was collected by vacuum filtration. The filtrate was concentration and purified by silica gel chromatography (eluting with Hexanes/ethyl acetate-4/1) to yield additional product. The material was combined to give tert-butyl 1-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (2.46 g, 83% yield).

Workup

  1. washwashed with a 10% aqueous solution of lithium chloride (2×100 mL)
  2. washwashed with water (100 mL)
  3. washwashed with brine (100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationConcentration
  6. customgave a crude product which
  7. customwas triturated with methanol
  8. filtrationThe resulting solid was collected by vacuum filtration
  9. concentrationconcentration
  10. custompurified by silica gel chromatography (eluting with Hexanes/ethyl acetate-4/1)
  11. customto yield additional product

Sources & evidence

ORD record
ord-af26589c19f14b6cb9ac8d49e2b525dc
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

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