Table 6. Condition Screening and Optimization of O-Debenzylation Reaction of Benzyl Dolutegravir 7 in Continuous Flowa.
| experiment name | total residence time (min) | solvent | temp (°C) | THF equivb | % yieldc |
|---|---|---|---|---|---|
| 1 | 30 | DCM | 38 | 5 | No rxn |
| 2 | 30 | DCM | 50 | 5 | 9 |
| 3 | 15 | DCM | 80 | 5 | 84 |
| 4 | 30 | DCM | 100 | 5 | 90 |
| 5 | 30 | ACN | 100 | 5 | 92 |
| 6 | 3 | ACN | 100 | 5 | 52 |
| 7 | 3 | ACN | 120 | 5 | 93 |
| 8 | 9 | ACN | 120 | 5 | 99 |
| 9 | 9 | ACN | 120 | 3 | 96 |
| 10 | 9 | ACN | 120 | 1 | 44 |
a
Standard conditions: Feed one—benzyl dolutegravir (0.1 M, 1 equiv), feed two—THF.
b
Molar equivalence.
c
Dolutegravir 1 percentage yield determined by HPLC using a synthetic standard.