Tetrahydrofuran → HCID 67455563, compound

HRID 469712Notes

Reaction equation

HRID 469712 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][CH2:10][C@@:9]2([CH3:16])[C:13]([OH:15])=O)=[CH:4][CH:3]=1.C(N(CC)CC)C.O1CCCC1.[NH2:29][C:30]1[CH:34]=[C:33]([C:35]([CH3:38])([CH3:37])[CH3:36])[O:32][N:31]=1>C(OCC)(=O)C>[C:35]([C:33]1[O:32][N:31]=[C:30]([NH:29][C:13]([C@:9]2([CH3:16])[CH2:10][CH2:11][CH2:12][N:8]2[C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)=[O:15])[CH:34]=1)([CH3:38])([CH3:37])[CH3:36]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-HCID 67457238HCID 67457238, compound

Product 1

HCID 67455563HCID 67455563, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A round bottomed flask is charged with (S)-1-(4-chloro-phenyl)-2-methyl-pyrrolidine-2-carboxylic acid (0.260 g; 1.085 mmol), triethylamine (0.529 mL; 3.798 mmol), and tetrahydrofuran (3 mL). Propylphorsphoric anhydride (50% in ethyl acetate) (0.678 mL; 1.139 mmol) is added dropwise and stirred for 30 minutes. 3-Amino-5-tertbutylisoxazole (0.152 g; 1.085 mmol) is added and the reaction is heated at 80° C. for 40 minutes in a microwave reactor. After this time, the reaction mixture is cooled to room temperature, diluted with ethyl acetate and washed with aqueous sodium bicarbonate solution. The aqueous is back extracted with ethyl acetate and the organics are combined and washed with brine, dried (Na2SO4), filtered and concentrated. Purification by preparative HPLC affords title compound. ESI m/z 362 [M+H]+

Workup

  1. temperatureAfter this time, the reaction mixture is cooled to room temperature
  2. washwashed with aqueous sodium bicarbonate solution
  3. extractionThe aqueous is back extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-cec670f3c4a64c83b55d607a608b4849
Source dataset
uspto-grants-2014_01
Patent number
US08629157B2

Reaction notes

Loading…