Tributylphosphine → (R)-4-butyl-1-[(S)-1-phenylethyl]pyrrolidin-2-one
Reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C(P(CCCC)CCCC)CCC.[C:30]1([C@@H:36]([NH:38][C:39](=[O:48])[CH2:40][C@H:41]([CH2:46]O)[CH2:42][CH2:43][CH2:44][CH3:45])[CH3:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])(O)=O.[Na+]>O1CCCC1>[CH2:42]([C@H:41]1[CH2:46][N:38]([C@H:36]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH3:37])[C:39](=[O:48])[CH2:40]1)[CH2:43][CH2:44][CH3:45]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of di-t-butyl azodicarboxylate (2.1 g, 9.1 mmol) in tetrahydrofuran (25 mL) under argon was added tributylphosphine (2.27 mL, 9.1 mmol). The mixture was stirred for 5 minutes and was added slowly to a solution of (R)-3-hydroxymethylheptanoic acid, (S)-1-phenylethylamide (1.84 g, 7.0 mmol) in dry THF (10 mL) at 0° C. The reaction was warmed up to rt and stirred overnight. Saturated NaHCO3 (100 mL) was added and the resulting mixture was extracted with CH2Cl2 (2×100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by flash column chromatography (silica gel, 1:4 EtOAc/hexanes) to afford 1.4 g (82%) of (R)-4-butyl-1-[(S)-1-phenylethyl]pyrrolidin-2-one as a colorless oil: 1H NMR (CDCl3) δ 7.33 (m, 5 H), 5.48 (q, 1 H), 3.06 (t, 1 H), 2.92 (t, 1 H), 2.53 (q, 1 H), 2.06 (m, 2 H), 1.51 (d, 3 H), 1.20-1.46 (m, 6 H), 0.88 (t, 3 H). MS(ES) m/e 246 [M+H]+.
Workup
- stirringstirred overnight
- extractionthe resulting mixture was extracted with CH2Cl2 (2×100 mL)
- dry with materialThe combined organic extracts were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by flash column chromatography (silica gel, 1:4 EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-391f00a634a94242b36b8f3b26c3f14c
- Source dataset
- uspto-grants-2008_11
- Patent number
- US07456211B2
Reaction notes
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