Potassium Fluoride → (R)-tert-Butyl 3-(3-(2-fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)ureido)pyrrolidine-1-carboxylate

HRID 1807761Notes

Reaction equation

HRID 1807761 reaction equation
[Si]([O:8][C:9]([C:18]1[CH:55]=[CH:54][C:21]([CH2:22][N:23]2[CH2:28][CH2:27][N:26]([C:29]([C:31]3[CH:36]=[CH:35][C:34]([NH:37][C:38](=[O:52])[NH:39][C@@H:40]4[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41]4)=[C:33]([F:53])[CH:32]=3)=[O:30])[CH2:25][CH2:24]2)=[CH:20][CH:19]=1)([C:14]([F:17])([F:16])[F:15])[C:10]([F:13])([F:12])[F:11])(C(C)(C)C)(C)C.[F-].[K+]>O1CCCC1>[F:53][C:33]1[CH:32]=[C:31]([C:29]([N:26]2[CH2:27][CH2:28][N:23]([CH2:22][C:21]3[CH:54]=[CH:55][C:18]([C:9]([OH:8])([C:10]([F:13])([F:11])[F:12])[C:14]([F:15])([F:16])[F:17])=[CH:19][CH:20]=3)[CH2:24][CH2:25]2)=[O:30])[CH:36]=[CH:35][C:34]=1[NH:37][C:38](=[O:52])[NH:39][C@@H:40]1[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:50])([CH3:49])[CH3:51])=[O:46])[CH2:41]1

Participants

4

Reactant 2

HCID 522689Potassium FluorideHCID 59175827(R)-tert-Butyl 3-(3-(4-(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazine-1-carbonyl)-2-fluorophenyl)ureido)pyrrolidine-1-carboxylate

Product 1

HCID 59175842(R)-tert-Butyl 3-(3-(2-fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)ureido)pyrrolidine-1-carboxylateYield 81.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a stirring solution of (R)-tert-butyl 3-(3-(4-(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazine-1-carbonyl)-2-fluorophenyl)ureido)-pyrrolidine-1-carboxylate (0.372 mmol, 300 mg) in tetrahydrofuran (10 mL) was added potassium fluoride (50% weight on celite) (3.72 mmol, 433 mg). The resulting suspension was heated to 80° C. for 16 hours. The reaction mixture was filtered through celite and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel (eluting with dichloromethane—5% methanol/95% dichloromethane gradient) to afford the title compound (210 mg). MS (ESI) m/z 692.3 [M+H]+

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. concentrationconcentrated under vacuum
  3. customThe resulting residue was purified by column chromatography on silica gel (eluting with dichloromethane—5% methanol/95% dichloromethane gradient)

Sources & evidence

ORD record
ord-c9b0c79c9ac7478393bd4658b1c2ff24
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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