1,2-Dichloroethane → HCID 69837847, compound

HRID 352710Notes

Reaction equation

HRID 352710 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([CH2:23][O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:10][N:9]=[C:8]([C@@H:11]([NH:15][C:16]([O:18]C(C)(C)C)=O)[CH:12]([CH3:14])[CH3:13])[CH2:7]1)=[O:5])[CH3:2].C(O)(C(F)(F)F)=O.C(Cl)CCl.[CH:42]1[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:45]=[CH:44][C:43]=1C(O)=O.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1([CH2:23][O:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[O:10][N:9]=[C:8]([C@@H:11]([NH:15][C:16]([C:44]2[CH:43]=[CH:42][C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[CH:45]=2)=[O:18])[CH:12]([CH3:13])[CH3:14])[CH2:7]1)=[O:5])[CH3:2]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 71232-Naphthoic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 69838992HCID 69838992, compound

Product 1

HCID 69837847HCID 69837847, compoundYield 90.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-{(1S)-1-(t-butoxycarbonylamino)-2-methyl-propyl}-5-phenoxymethyl-4,5-dihydro-isoxazole-5-carboxylic acid ethyl ester (2.00 g, 4.76 mmol) in dry CH2Cl2 (10 mL) at 0° C. under N2 was treated with TFA (6 mL) and stirred for 1.5 h. After removal of volatiles, the residue was taken up with ethyl acetate (200 mL), washed with sat'd NaHCO3(100 mL×2), dried (anh Na2SO4), filtered and concentrated. To a solution of the crude product, EDC (1.09 g, 1.2 eq), 2-naphthoic acid (983 mg, 1.2 eq) and HOBt (771 mg, 1.2 eq) in DMF (20 mL) at 0° C. was added triethylamine (663 uL, 1.0 eq). The reaction was stirred overnight at room temperature. After removal of volailes in vacuo, the residue was taken up with ethyl acetate (250 mL), washed with water(100 mL), sat'd NaHCO3 (100 mL×2), dried (anh Na2SO4), filtered and concentrated. Flash chromatography with 25-33% ethyl acetate/hexanes gave 2.04 g (90%) of the title compound.

Workup

  1. customAfter removal of volatiles
  2. washwashed with sat'd NaHCO3(100 mL×2)
  3. dry with materialdried (anh Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. stirringThe reaction was stirred overnight at room temperature
  7. customAfter removal of volailes in vacuo
  8. washwashed with water(100 mL), sat'd NaHCO3 (100 mL×2)
  9. dry with materialdried (anh Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-6dc83af556654f888e2b4e41bcd4d9b3
Source dataset
uspto-grants-2004_06
Patent number
US06747050B1

Reaction notes

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