Tetrabutylammonium Fluoride → tert-Butyl {4-[(2R,3R)-1-(4-fluorophenyl)-3-({[2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)-4-oxoazetidin-2-yl]phenoxy}acetate

HRID 254090Notes

Reaction equation

HRID 254090 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C@@H:9]([C:43]2[CH:57]=[CH:56][C:46]([O:47][CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[CH:45][CH:44]=2)[C@@H:10]([S:25][CH2:26][C:27]2([C:35]3[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=3)[O:32][CH2:31][C:30]([CH3:34])([CH3:33])[CH2:29][O:28]2)[C:11](=[O:24])N2[C@@H](C3C=CC=CC=3)COC2=O)=[CH:4][CH:3]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:11](=[O:24])[C@H:10]([S:25][CH2:26][C:27]3([C:35]4[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=4)[O:28][CH2:29][C:30]([CH3:33])([CH3:34])[CH2:31][O:32]3)[C@H:9]2[C:43]2[CH:44]=[CH:45][C:46]([O:47][CH2:48][C:49]([O:51][C:52]([CH3:53])([CH3:54])[CH3:55])=[O:50])=[CH:56][CH:57]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 86619089tert-Butyl (4-{(1S,2R)-1-[(4-fluorophenyl)amino]-2-({[2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)-3-oxo-3-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]propyl}phenoxy)acetate

Product 1

HCID 86619090tert-Butyl {4-[(2R,3R)-1-(4-fluorophenyl)-3-({[2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)-4-oxoazetidin-2-yl]phenoxy}acetateYield 41%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

tert-Butyl (4-{(1S,2R)-1-[(4-fluorophenyl)amino]-2-({[2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)-3-oxo-3-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]propyl}phenoxy)acetate (2.0 g, 2.5 mmol) was dissolved in dry toluene (200 ml) and heated to 90° C. under inert atmosphere. N,O-Bis(trimethylsilyl)acetamide (BSA, 1.8 ml, 7.5 mmol) was added and the mixture was stirred at 90° C. for one hour. The mixture was cooled to 45° C. and tetrabutylammonium fluoride (TBAF, 150 mg) was added and the mixture was stirred at 45° C. for two hours. The mixture was concentrated under reduced pressure and filtered through a short column of silica (hexane:EtOAc 4:1). Purification of the crude oil by flash-chromatography (hexane:EtOAc 5:1) gave 0.65 g (41%) of the title compound as a yellow solid. 1H-NMR (CDCl3, 200 MHz): δ 0.6 (s, 3H), 1.3 (s, 3H), 1.5 (s, 9H), 3.0-3.2 (m, 2H), 3.3-3.5 (m, 4H), 3.8 (s, 3H), 4.0 (d, 1H), 4.5 (s, 2H), 4.8 (d, 1H), 6.8-7.0 (m, 6H), 7.2-7.4 (m, 6H).

Workup

  1. temperatureThe mixture was cooled to 45° C.
  2. stirringthe mixture was stirred at 45° C. for two hours
  3. concentrationThe mixture was concentrated under reduced pressure
  4. filtrationfiltered through a short column of silica (hexane:EtOAc 4:1)
  5. customPurification of the crude oil by flash-chromatography (hexane:EtOAc 5:1)

Sources & evidence

ORD record
ord-c977ec3362e248edb9e9dbf3070e353f
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

Loading…