Tetrabutylammonium Fluoride → (S)-tert-butyl 4-(4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-hydroxypentanoyl)piperazine-1-carboxylate

HRID 409796Notes

Reaction equation

HRID 409796 reaction equation
[Si]([O:8][CH2:9][C@@H:10]([N:28]([CH3:41])[C:29]([NH:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:34]=1[Cl:40])=[O:30])[CH2:11][CH2:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=[O:14])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:40][C:34]1[C:35]([F:39])=[CH:36][CH:37]=[CH:38][C:33]=1[CH2:32][NH:31][C:29](=[O:30])[N:28]([C@H:10]([CH2:9][OH:8])[CH2:11][CH2:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:17][CH2:16]1)=[O:14])[CH3:41]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57947925(S)-tert-butyl 4-(5-(tert-butyldimethylsilyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoyl)piperazine-1-carboxylate

Product 1

HCID 57947492(S)-tert-butyl 4-(4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-hydroxypentanoyl)piperazine-1-carboxylateYield 105.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-tert-butyl 4-(5-(tert-butyldimethylsilyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoyl)piperazine-1-carboxylate (14 g, 22.8 mmol) in THF (70 mL) was added TBAF (1M, 34.2 mL, 34.2 mmol). The reaction mixture was stirred at RT for 1 h and concentrated. The residue was dissolved in EtOAc (500 mL). The organic mixture was washed with 2% citric acid, NaOH (0.2 N), and brine, dried over Na2SO4, filtered, and concentrated to give (S)-tert-butyl 4-(4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-hydroxypentanoyl)piperazine-1-carboxylate (12.1 g, crude), which was used without further purification. LRMS (M+H) m/z 501.2.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in EtOAc (500 mL)
  3. washThe organic mixture was washed with 2% citric acid, NaOH (0.2 N), and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4cc437fb05084fef982ebaa868661e15
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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