Derbyshire 105 (Fletcher 5-28) and 23 for 0 need a further 447 runs to beat Nottinghamshire 256 and 318 (Hameed 94, Duckett 87, Clarke 53, Hudson-Prentice 4-40)
Nottinghamshire are on course to end a first-class drought stretching back to 2018 after dominating the second day of the LV= Insurance County Championship match against Derbyshire at Derby.
Luke Fletcher completed a five-wicket haul as Derbyshire were skittled for 105 before half-centuries from Haseeb Hameed, Ben Duckett and Joe Clarke drove home their advantage.
Hameed scored 94 from 142 balls and Duckett, who passed 25 for the first time this season, made 87 off 101 balls with Clarke contributing 53 as Notts scented their first victory in red-ball cricket for nearly three years.
Although they lost five wickets for 10 runs to be bowled out for 318 with Fynn Hudson-Prentice taking 4 for 40, Derbyshire were set a daunting target of 470 and reached 23 for 0 at the close.
Derbyshire's first objective at the start of the day was to reach the follow-on target of 107 but they came up short with Fletcher claiming the last two wickets.
Ben Aitchison went in the second over of the day, edging to third slip with no addition to the overnight score but Brooke Guest and Sam Conners resisted for another eight overs.
Fletcher bowled Guest off a glove but with three days left in the game, Steven Mullaney decided against enforcing the follow-on.
By lunch, Notts had extended the lead to 211 for the loss of Ben Slater who saw his hopes of a third consecutive century ended when a ball from Luis Reece came off a pad and dislodged the leg bail.
The afternoon was dominated by Hameed and Duckett who plundered 157 in 29 overs to extinguish any chance Derbyshire had of staying in the game.
Duckett looked set to end a lean run with a century until he edged Hudson-Prentice low to first slip and Hameed's ambitions of a third hundred in four innings ended in the first over after tea when he was bowled trying to cut Matt Critchley.
Nottinghamshire's innings ended chaotically after Clarke fell to an acrobatic catch at midwicket by Tom Wood with the last five wickets falling in five overs.
That left Derbyshire with 40 minutes to bat which Reece and Wood negotiated with few alarms although it would take a remarkable effort to deny Notts that long overdue victory.
Notts vs Derbyshire