Isopropanol → 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

HRID 254089Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([CH2:17][S:18][CH2:19][C:20]([N:22]3[C@@H:26]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:25][O:24][C:23]3=[O:33])=[O:21])[O:14][CH2:13][C:12]([CH3:16])([CH3:15])[CH2:11][O:10]2)=[CH:5][CH:4]=1.[F:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]=[CH:42][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)=[CH:37][CH:36]=1.C(N(C(C)C)C(C)C)C.C(O)(C)C>C(Cl)Cl.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4].Cl[Ti](Cl)(Cl)Cl.O>[F:34][C:35]1[CH:36]=[CH:37][C:38]([NH:41][C@@H:42]([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)[C@@H:19]([S:18][CH2:17][C:9]2([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[O:14][CH2:13][C:12]([CH3:16])([CH3:15])[CH2:11][O:10]2)[C:20](=[O:21])[N:22]2[C@@H:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:25][O:24][C:23]2=[O:33])=[CH:39][CH:40]=1

Participants

Conditions

Temperature: -30 °C

Procedure

Tetraisopropyl orthotitanate (0.31 ml, 1.06 mmol) was added to a solution of TiCl4 (1M in CH2Cl2, 3.18 ml, 3.18 mmol) in CH2Cl2 (50 ml) at 0° C. under inert atmosphere. The mixture was stirred for ten minutes. (4S)-3-[({[2-(4-Methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)acetyl]-4-phenyl-1,3-oxazolidin-2-one (2.00 g, 4.24 mmol) in dry CH2Cl2 (50 ml) was added dropwise over 20 minutes. The mixture was stirred for ten minutes. tert-Butyl (4-{[(4-fluorophenyl)imino]methyl}phenoxy)acetate (2.79 g, 8.48 mmol) in dry CH2Cl2 (50 ml) was added dropwise over 30 minutes. The mixture was cooled to −30° C. and stirred for 20 minutes. Ethyl diisopropyl amine (1.45 ml, 8.48 mmol) in 10 ml dry CH2Cl2 was added dropwise over ten minutes and the mixture was stirred at −30° C. for five hours. The mixture was cooled to −78° C. Isopropanol (60 ml) was added and the temperature was allowed to rise overnight. H2O (100 ml) was added and the mixture was stirred for 20 minutes and extracted twice with diethyl ether. The combined organic layers were washed with water, dried (MgSO4) and concentrated under reduced pressure. Purification by flash-chromatography (hexane:EtOAc 3:1) afforded 2.00 g (59%) 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), 2.6-2.9 (m, 2H), 3.3-3.5 (m, 4H), 3.8 (s, 3H), 4.1-4.3 (m, 2H), 4.5 (s, 2H), 4.6-4.8 (m, 2H), 5.0-5.4 (s, broad, 1H), 5.4 (m, 1H), 5.7 (d, 1H), 6.4 (m, 2H), 6.6-6.8 (m, 4H), 6.8-7.0 (m, 4H), 7.1-7.4 (m, 7H).

Workup

stirringThe mixture was stirred for ten minutes
stirringstirred for 20 minutes
stirringthe mixture was stirred at −30° C. for five hours
temperatureThe mixture was cooled to −78° C
stirringthe mixture was stirred for 20 minutes
extractionextracted twice with diethyl ether
washThe combined organic layers were washed with water
dry with materialdried (MgSO4)
concentrationconcentrated under reduced pressure
customPurification by flash-chromatography (hexane:EtOAc 3:1)

Sources & evidence

ORD record: ord-6ef8593fc0e84be2b4ad1eb3eca871c6
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07871998B2

Reaction notes

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