1,1-Dichloroethane → HCID 9801782, compound

HRID 1246564Notes

Reaction equation

HRID 1246564 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.[CH3:10][C@@:11]1([CH2:14][O:15][C:16]2[CH:17]=[C:18]([C:22]3[C:26]4[S:27][CH:28]=[CH:29][C:25]=4[O:24][N:23]=3)[CH:19]=[CH:20][CH:21]=2)[CH2:13][O:12]1.ClC(Cl)C>C(O)C>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:7][CH2:10][C@:11]([CH3:13])([OH:12])[CH2:14][O:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]3[C:26]4[S:27][CH:28]=[CH:29][C:25]=4[O:24][N:23]=3)[CH:17]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 63651,1-DichloroethaneHCID 673264-FluorobenzylamineHCID 11312234HCID 11312234, compound

Product 1

HCID 9801782HCID 9801782, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Add a solution of 4-fluorobenzylamine (Aldrich Chemical Company) in ethanol (3 mL, 0.2774 M, 1.77 equivalents) to a reaction tube. Add ethanol (3 mL) to the reaction tube and then add a solution of (S)-3-[3-(2-methyloxiranylmethoxy)phenyl]thieno[2,3-d]isoxazole (example 7, 1.38 mL, 0.337 M) and dichloroethane. Shake the reaction mixture under argon at reflux temperature overnight in a Bohdan apparatus. Cool and concentrate to remove the solvent. Purify the residue by flash chromatography (silica gel) eluting in step gradient fashion sequentially with 1%, 3%, 6%, and 10% methanol in dichloromethane. Combine and concentrate the desired fractions to give the title compound (0.18 g), LC/MS (APCI, condition 6) m/e 413 (MH+), retention time 2.23 min. Preparation of a larger sample and conversion to the hydrochloride salt is described as example 102.

Workup

  1. temperatureShake the reaction mixture under argon at reflux temperature overnight in a Bohdan apparatus
  2. temperatureCool
  3. concentrationconcentrate
  4. customto remove the solvent
  5. customPurify the residue by flash chromatography (silica gel)
  6. washeluting in step gradient fashion sequentially with 1%, 3%, 6%, and 10% methanol in dichloromethane
  7. concentrationCombine and concentrate the desired fractions

Sources & evidence

ORD record
ord-eeff00429a7e49c48cbc7b79abe6c4d7
Source dataset
uspto-grants-2006_10
Patent number
US07125903B1

Reaction notes

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