tert-Butyl hydroperoxide → (+)-(3R)-[3-Ethyl-3-(2-Methoxy-3-methoxymethoxymethyl-pyridin-4-yl)oxiranyl]methanol
Reaction equation
[CH3:1][O:2][C:3]1[C:8]([CH2:9][O:10][CH2:11][O:12][CH3:13])=[C:7]([C:14]([CH2:18][CH3:19])=[CH:15][CH2:16][OH:17])[CH:6]=[CH:5][N:4]=1.C([C@@](C([O-])=O)(O)[C@@](CC)(O)C([O-])=[O:25])C.C(OO)(C)(C)C>C(Cl)Cl.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[CH2:18]([C@:14]1([C:7]2[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[C:8]=2[CH2:9][O:10][CH2:11][O:12][CH3:13])[O:25][CH:15]1[CH2:16][OH:17])[CH3:19]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
Following the procedure in Example 5, the reaction was carried out with 5b (0.80 g, 3 mmol), Ti(OiPr)4 (0.71 mL, 2.4 mmol), diethyl-L(+)-tartrate (0.51 mL, 3 mmol), tBuOOH (0.95 mL, 5.0-6.0M in decane) and 4 Å molecular sieves (241 mg) in dry CH2Cl2 for 24 h to afford 6b as a yellow oil (754 mg, 89%) with 96% ee. The crude product was sufficiently pure for the subsequent reaction. Epoxide 6b was analyzed for enantiomeric purity using a Chiralcel OD-H column with 98:2 hexane/iPrOH as the eluent with the racemate as the standard. IR (CH2Cl2, NaCl,cm−1) 3408, 2980, 1765, 1607, 1457, 1410, 1393, 1266, 1040, 742, 546; 1H NMR (300 MHz, CDCl3) δ0.92 (t, J=7.6 Hz, 3H), 1.82 (m, 1H), 1.99 (m, 1H), 3.24 (t, J=5.8 Hz, 1H), 3.46 (s, 3H), 3.90 (m, 2H), 3.99 (s, 3H), 4.71 (s, 2H), 4.73 (s, 2H), 6.93 (d,J=5.2 Hz, 1H), 8.12 (d, J=5.2 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ9.41, 25.73, 25.98, 54.06, 55.82, 60.80, 61.33, 63.72, 64.72, 96.70, 116.46, 116.83, 146.60, 150.98, 163.10; HRMS (EI) m/z calcd for C14H22NO5 (M+H) 284.1498, found 284.1507; LRMS (EI) m/z 284(M+H, 58), 190(100), 178(73), 162(27), 148(27), 77(13); [α]D23=+65.6(c=0.25, CH2Cl2).
Sources & evidence
- ORD record
- ord-09662917fdbd4ec58bf734c874d4b9b2
- Source dataset
- uspto-grants-2004_04
- Patent number
- US06723853B2
Reaction notes
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