Potassium Fluoride → (S)-1-(2-Fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-piperazine-1-carbonyl)phenyl)-3-(1-hydroxybutan-2-yl)urea

HRID 1807725Notes

Reaction equation

[Si]([O:8][C:9]([C:18]1[CH:48]=[CH:47][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]([NH:40][C@@H:41]([CH2:44][CH3:45])[CH2:42][OH:43])=[O:39])=[C:33]([F:46])[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:46][C:33]1[CH:32]=[C:31]([C:29]([N:26]2[CH2:25][CH2:24][N:23]([CH2:22][C:21]3[CH:20]=[CH:19][C:18]([C:9]([OH:8])([C:14]([F:16])([F:15])[F:17])[C:10]([F:13])([F:11])[F:12])=[CH:48][CH:47]=3)[CH2:28][CH2:27]2)=[O:30])[CH:36]=[CH:35][C:34]=1[NH:37][C:38]([NH:40][C@@H:41]([CH2:44][CH3:45])[CH2:42][OH:43])=[O:39]

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirring solution of (S)-1-(4-(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazine-1-carbonyl)-2-fluorophenyl)-3-(1-hydroxybutan-2-yl)urea (0.303 mmol, 215 mg) in tetrahydrofuran (1 mL) was added potassium fluoride (50% weight on celite) (1.517 mmol, 176 mg). The resulting suspension was heated to 80° C. for 48 hours. The reaction mixture was filtered through celite and concentrated under vacuum. The resulting residue was purified by SCX chromatography to afford the title compound (132.4 mg).

Workup

filtrationThe reaction mixture was filtered through celite
concentrationconcentrated under vacuum
customThe resulting residue was purified by SCX chromatography

Sources & evidence

ORD record: ord-2dfad7203da5422e86e0f6c63f8280cd
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08357679B2

Reaction notes

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