Table 1. Optimization of Reaction Conditions for Hydrogenation and Reduction of Compound 3a.
| entry | cat. (mg) | base (equiv) | solvent (v:v) | temp. (°C) | time (h) | yield (%)b | 4:Imp-3c |
|---|---|---|---|---|---|---|---|
| 1 | 10%wt Pd/C (5.0) | pyridine (1.0) | MeOH/DCM (1:1) | 25 | 12 | 64 | 88:12 |
| 2 | 10%Pd/CaCO3 (5.0) | pyridine (1.0) | MeOH/DCM (1:1) | 25 | 12 | 47 | 80:20 |
| 3 | PdCl2(PPh3)2 (5.0) | pyridine (1.0) | MeOH/DCM (1:1) | 25 | 12 | 0 | - |
| 4 | Pd(PPh3)4 (5.0) | pyridine (1.0) | MeOH/DCM (1:1) | 25 | 12 | 0 | - |
| 5 | Pd–Cu NWs (5.0) | pyridine (1.0) | MeOH/DCM (1:1) | 25 | 12 | 72 | 92:8 |
| 6 | Pd–Cu NWs (5.0) | pyridine (1.0) | MeOH/DCM (2:1) | 25 | 12 | 76 | 92:8 |
| 7 | Pd–Cu NWs (5.0) | pyridine (1.0) | MeOH/DCM (4:1) | 25 | 12 | 84 | 94:6 |
| 8 | Pd–Cu NWs (5.0) | pyridine (1.0) | MeOH/DCM (5:1) | 25 | 12 | 69 | 93:7 |
| 9 | Pd–Cu NWs (5.0) | pyridine (1.0) | MeOH/DCM (1:2) | 25 | 12 | 68 | 82:13 |
| 10 | Pd–Cu NWs (5.0) | pyridine (1.0) | MeOH | 25 | 12 | 75 | 85:15 |
| 11 | Pd–Cu NWs (5.0) | pyridine (1.0) | DCM | 25 | 12 | 40 | 88:12 |
| 12 | Pd–Cu NWs (5.0) | CH3COONH4 (1.0) | MeOH/DCM (4:1) | 25 | 12 | 72 | 90:10 |
| 13 | Pd–Cu NWs (5.0) | Et3N (1.0) | MeOH/DCM (4:1) | 25 | 12 | 89 | 93:7 |
| 14 | Pd–Cu NWs (5.0) | cholamine (1.0) | MeOH/DCM (4:1) | 25 | 12 | 78 | 89:11 |
| 15 | Pd–Cu NWs (6.0) | Et3N (1.0) | MeOH/DCM (4:1) | 25 | 12 | 92 | 93:7 |
| 16 | Pd–Cu NWs (7.0) | Et3N (1.0) | MeOH/DCM (4:1) | 25 | 12 | 90 | 93:7 |
| 17 | Pd–Cu NWs (6.0) | Et3N (0.75) | MeOH/DCM (4:1) | 25 | 12 | 84 | 93:7 |
| 18 | Pd–Cu NWs (6.0) | Et3N (1.2) | MeOH/DCM (4:1) | 25 | 12 | 91 | 93:7 |
| 19 | Pd–Cu NWs (6.0) | Et3N (1.0) | MeOH/DCM (4:1) | 40 | 12 | 83 | 90:10 |
| 20 | Pd–Cu NWs (6.0) | Et3N (1.0) | MeOH/DCM (4:1) | 10 | 12 | 92 | 97:3 |
| 21 | Pd–Cu NWs (6.0) | Et3N (1.0) | MeOH/DCM (4:1) | 10 | 9 | 92 | 97:3 |
| 22 | Pd–Cu NWs (6.0) | Et3N (1.0) | MeOH/DCM (4:1) | 10 | 7 | 83 | 97:3 |
| 23d | Pd–Cu NWs (3 g) | Et3N (13 g) | MeOH/DCM (4:1) | 10 | 18 | 91 | 96.8:3.2 |
| 24e | Pd–Cu NWs (6.0) | Et3N (1.0) | MeOH/DCM (4:1) | 10 | 9 | 91/89/85 | 97:3 |
a
Reaction conditions: compound 3 (0.26 mmol, 0.1 g), catalyst, 1 atm of H2, base, solvent: 5 mL.
b
The yield is crude (4 and Imp-3).
c
The ratio of the isomer was determined by HPLC equipped with an RI detector.
d
Compound 3 (50 g), solvent: 500 mL.
e
Recycled three times: 91% (run 1), 89% (run 2), and 85% (run 3).