Ammonium Chloride → 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

HRID 254101Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:16][S:17][CH2:18][C:19]([N:21]3[C@@H:25]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:24][O:23][C:22]3=[O:32])=[O:20])[O:13][CH2:12][C:11]([CH3:15])([CH3:14])[CH2:10][O:9]2)=[CH:4][CH:3]=1.[Cl:33][C:34]1[CH:39]=[CH:38][C:37](/[N:40]=[CH:41]/[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)=[CH:36][CH:35]=1.C(N(C(C)C)C(C)C)C.[NH4+].[Cl-]>C(Cl)Cl.[Cl-].[Na+].O.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4].Cl[Ti](Cl)(Cl)Cl.C(O)(C)C>[Cl:33][C:34]1[CH:35]=[CH:36][C:37]([NH:40][C@@H:41]([C:42]2[CH:43]=[CH:44][C:45]([O:46][CH2:47][C:48]([O:50][C:51]([CH3:52])([CH3:53])[CH3:54])=[O:49])=[CH:55][CH:56]=2)[C@@H:18]([S:17][CH2:16][C:8]2([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[O:9][CH2:10][C:11]([CH3:14])([CH3:15])[CH2:12][O:13]2)[C:19](=[O:20])[N:21]2[C@@H:25]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:24][O:23][C:22]2=[O:32])=[CH:38][CH:39]=1

Participants

Conditions

Temperature: -40 °C

Procedure

Tetraisopropyl orthotitanate (0.23 ml, 0.77 mmol) was added to a solution of TiCl4 (1M in CH2Cl2, 2.25 ml, 2.25 mmol) in CH2Cl2 (22 ml) at 0° C. under inert atmosphere. The mixture was stirred for ten minutes. (4S)-3-[({[2-(4-Chlorophenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)acetyl]-4-phenyl-1,3-oxazolidin-2-one (1.44 g, 3.03 mmol) in dry CH2Cl2 (25 ml) was added dropwise over 45 minutes and the mixture was stirred for ten minutes. tert-Butyl (4-{(E)-[(4-chlorophenyl)imino]methyl}phenoxy)acetate (2.09 g, 6.04 mmol) in dry CH2Cl2 (25 ml) was added dropwise over 80 minutes. The mixture was cooled to −40° C. and stirred for 20 minutes. Ethyl diisopropyl amine (1.03 ml, 6.02 mmol) was added dropwise over 40 minutes and the mixture was stirred at −40° C. for ten minutes. The mixture was cooled to −78° C. and isopropanol (80 ml) was added. The temperature was allowed to reach room temperature over three hours. NH4Cl (10%, 80 ml) was added and the mixture was stirred for 35 minutes. Brine (200 ml) was added and the mixture was extracted twice with 400 ml diethyl ether. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. Purification by flash-chromatography (10%-20% EtOAc in hexane) afforded 1.69 g (65%) of the title compound as a white solid. 1H-NMR (CDCl3, 200 MHz): δ 0.65 (s, 3H), 1.3 (s, 3H), 1.5 (s, 9H), 2.6-2.9 (m, 2H), 3.4 (m, 4H), 4.2 (m, 1H), 4.5 (s, 2H), 4.64-8 (m, 2H), 5.3 (m, 1H), 5.7 (d, 1H), 6.4 (m, 2H), 6.7-7.4 (m, 15H).

Workup

stirringthe mixture was stirred for ten minutes
stirringstirred for 20 minutes
stirringthe mixture was stirred at −40° C. for ten minutes
temperatureThe mixture was cooled to −78° C.
stirringthe mixture was stirred for 35 minutes
extractionthe mixture was extracted twice with 400 ml diethyl ether
dry with materialThe combined organic layers were dried (MgSO4)
concentrationconcentrated under reduced pressure
customPurification by flash-chromatography (10%-20% EtOAc in hexane)

Sources & evidence

ORD record: ord-bb6a0f2644be4caebc5eafb815c1a3f9
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07871998B2

Reaction notes

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