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

HRID 254102Notes

Reaction equation

HRID 254102 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C@@H:9]([C:42]2[CH:56]=[CH:55][C:45]([O:46][CH2:47][C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[CH:44][CH:43]=2)[C@@H:10]([S:25][CH2:26][C:27]2([C:35]3[CH:40]=[CH:39][C:38]([Cl:41])=[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>[Cl: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:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=4)[O:28][CH2:29][C:30]([CH3:33])([CH3:34])[CH2:31][O:32]3)[C@H:9]2[C:42]2[CH:43]=[CH:44][C:45]([O:46][CH2:47][C:48]([O:50][C:51]([CH3:53])([CH3:54])[CH3:52])=[O:49])=[CH:55][CH:56]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 86619096tert-Butyl (4-{(1S,2R)-1-[(4-chlorophenyl)amino]-2-({[2-(4-chlorophenyl)-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 86619095tert-Butyl {4-[(2R,3R)-1-(4-chlorophenyl)-3-({[2-(4-chlorophenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)-4-oxoazetidin-2-yl]phenoxy}acetate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

tert-Butyl (4-{(1S,2R)-1-[(4-chlorophenyl)amino]-2-({[2-(4-chlorophenyl)-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 (1.69 g, 2.06 mmol) was dissolved in dry toluene (140 ml) and heated to 90° C. under inert atmosphere. N,O-Bis(trimethylsilyl)acetamide (BSA, 1.48 ml, 6.05 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, 0.1 g) was added and the mixture was stirred at 45° C. for one hour and at room temperature overnight. The mixture was concentrated under reduced pressure and purified by flash-chromatography (10%-20% EtOAc in hexane). This afforded 0.84 g (61%) of the title compound as a white solid. 1H-NMR (CDCl3, 200 MHz): δ 0.6 (s, 3H), 1.2 (s, 3H), 1.5 (s, 9H), 2.9-3.1 (t, broad, 2H), 3.4 (s, 4H), 4.0 (s, 1H), 4.5 (s, 2H), 4.8 (s, 1H), 6.9 (d, 2H), 7.2-7.4 (m, 10H).

Workup

  1. temperatureThe mixture was cooled to 45° C.
  2. stirringthe mixture was stirred at 45° C. for one hour and at room temperature overnight
  3. concentrationThe mixture was concentrated under reduced pressure
  4. custompurified by flash-chromatography (10%-20% EtOAc in hexane)

Sources & evidence

ORD record
ord-c87f241654104e24862b6a21dd4cfb95
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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