2-Amino-2-phenylethan-1-ol → (3S,7aS)-7a-cyclopropyl-3-phenyltetrahydropyrrolo[2,1-b]oxazol-5(6H)-one

HRID 406487Notes

Reaction equation

HRID 406487 reaction equation
[NH2:1][C@@H:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH2:3][OH:4].[CH:11]1([C:14](=O)[CH2:15][CH2:16][C:17](O)=[O:18])[CH2:13][CH2:12]1>C1(C)C=CC=CC=1.CCOC(C)=O>[CH:11]1([C@@:14]23[CH2:15][CH2:16][C:17](=[O:18])[N:1]2[C@@H:2]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH2:3][O:4]3)[CH2:13][CH2:12]1

Participants

5

Reactant 2

HCID 1347972-Amino-2-phenylethan-1-olHCID 162137294-Cyclopropyl-4-oxobutanoic acid

Product 1

HCID 59764671(3S,7aS)-7a-cyclopropyl-3-phenyltetrahydropyrrolo[2,1-b]oxazol-5(6H)-oneYield 75.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (S)-2-amino-2-phenylethanol (2.28 g, 16.6 mmol) and 4-cyclopropyl-4-oxobutanoic acid (1.97 g, 13.8 mmol) in toluene (35 mL) was heated at reflux for about 6 h. The reaction mixture was cooled to room temperature and diluted with EtOAc, washed with aqueous HCl (1.0 N), saturated NaHCO3, brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified on a Biotage silica gel column eluting with heptane/EtOAc (3:2) to afford (3S,7aS)-7a-cyclopropyl-3-phenyltetrahydropyrrolo[2,1-b]oxazol-5(6H)-one (2.54 g, 10.4 mmol) as a bright yellow needle-like solid. RP-HPLC (Table 1, Method a) Rt 1.77 min; m/z: (M+H)+ 244.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for about 6 h
  3. washwashed with aqueous HCl (1.0 N), saturated NaHCO3, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on a Biotage silica gel column
  8. washeluting with heptane/EtOAc (3:2)

Sources & evidence

ORD record
ord-5b62b187d7964388890c08ebf9a8995b
Source dataset
uspto-grants-2014_06
Patent number
US08754107B2

Reaction notes

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