Synthesis of phenylpiperazine 4 and analogs 1, 2.1-2.21 and 2.33-2.35
a.
Synthesis of phenylpiperazine 4 and analogs 1, 2.1-2.21 and 2.33-2.35
a
.
aReagents and conditions: (a) 3-Trifluoromethylphenylbromide, Pd(OAc)2, P(tBu)3, NaOtBu, o-xylene, 120°C, 17 h, 77%. (b) Appropriate carboxylic acid, TBTU, DIPEA, dry DMF, rt, 20 h, 51-92%. (c) Appropriate acid chloride (except for the synthesis of 2.32: benzyl carbonochloridate), Et3N, dry dichloromethane, rt, 30 min, 71-78%. (d) Benzenesulfonyl chloride, Et3N, dry dichloromethane, rt, 30 min, 71%. (e) BnBr, Et3N, dry dichloromethane, rt, 24 h, 57%. (f) Starting from (±)-endo-exo-1: LiAlH4, THF, rt, 72 h, 71%.