Allyl bromide → (+/-)-4-(alpha-(trans-4-allyl-2,5-dimethyl-1-piperazinyl)-5-(tert-butyldimethylsilyloxy)-2-fluorobenzyl)-N,N-diethylbenzamide

HRID 2258330Notes

Reaction equation

[CH3:1][C@H:2]1[CH2:7][NH:6][C@H:5]([CH3:8])[CH2:4][N:3]1[CH:9]([C:25]1[CH:37]=[CH:36][C:28]([C:29]([N:31]([CH2:34][CH3:35])[CH2:32][CH3:33])=[O:30])=[CH:27][CH:26]=1)[C:10]1[CH:15]=[C:14]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH:13]=[CH:12][C:11]=1[F:24].[CH2:38](Br)[CH:39]=[CH2:40].C(=O)([O-])[O-].[Na+].[Na+]>>[OH-:16].[NH4+:3].[CH2:40]([N:6]1[C@H:5]([CH3:8])[CH2:4][N:3]([CH:9]([C:25]2[CH:37]=[CH:36][C:28]([C:29]([N:31]([CH2:34][CH3:35])[CH2:32][CH3:33])=[O:30])=[CH:27][CH:26]=2)[C:10]2[CH:15]=[C:14]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH:13]=[CH:12][C:11]=2[F:24])[C@@H:2]([CH3:1])[CH2:7]1)[CH:39]=[CH2:38]

Participants

Reactant 3

HCID 7841Allyl bromide

HCID 10340Sodium Carbonate

HCID 69941891(+/-)-4-(alpha-(trans-2,5-dimethyl-1-piperazinyl)-5-(tert-butyldimethylsilyloxy)-2-fluorobenzyl)-N,N-diethylbenzamide

Product 2

HCID 14923Ammonium Hydroxide

HCID 69942360(+/-)-4-(alpha-(trans-4-allyl-2,5-dimethyl-1-piperazinyl)-5-(tert-butyldimethylsilyloxy)-2-fluorobenzyl)-N,N-diethylbenzamideYield 78%

Procedure

The benzhydrylpiperazine from above (0.44 g, 0.83 mmol) was treated with allyl bromide (0.074 mL, 0.85 mmol) and anhydrous sodium carbonate (0.44 g, 4.2 mmol) as in Example 1. The product was purified by preparative thin layer chromatography (silica gel with dichioromethane:methanol:ammonium hydroxide/90:10:1)to give 0.37 g (78%) of (±)-4-(α-(trans-4-allyl-2,5-dimethyl-1-piperazinyl)-5-(tert -butyldimethylsilyloxy)-2-fluorobenzyl)-N,N-diethylbenzamide as a yellow oil. Reaction with tetraethylammonium fluoride hydrate in acetonitrile as in Example 1, followed by chromatography on silica gel with dichloromethane:methanol/4:1 gave 0.24 g (77%) of (±)-4-(α-(trans-4-allyl -2,5-dimethyl-1 -piperazinyl)-2-fluoro-5-hydroxybenzyl)-N,N-diethylbenzamide as a light amber resin. NMR (CDCl3): δ1.0-1.3 (m, 12H); 2.0-2.3 (m, 2H); 2.5-3.05 (m, 5H); 3.2-3.6 (br m, 5H); 5.1-5.3 (m, 2H); 5.25 and 5.55 (s, 1H); 5.7-6.0 (m, 1H); 6.5-7.2 (m, 3H); 7.25 (d, J=8 Hz, 2H); 7.4 (d, J=8 Hz, solution of the product in absolute ethanol was titrated to pH 4 with ethanolic hydrochloric acid, concentrated and treated with diethyl ether to precipitate 0.21 g (63%) of the monohydrochloride as an off-white powder. Calc. for C27H36FN3O2HCl 1.25 H2O: C, 63.27; H, 7.77; N, 8.20; Cl, 6.92. Found: C, 63.33; H, 7.78; N, 8.24; Cl, 7.00. Mass spectrum (Cl-CH4) m/z: 454 (M+1, 100%), 453 (M, 6%), 300 (17%), 153 (95%).

Workup

customThe product was purified by preparative thin layer chromatography (silica gel with dichioromethane

Sources & evidence

ORD record: ord-627930f4384a4a56ad93453d5d862eae
Source dataset: uspto-grants-1997_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05658908

Reaction notes

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