Hydrochloric Acid → (R)-4-[2-(4-Heptyloxy-phenyl)-ethyl]-4-methyl-2-oxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester

HRID 12583Notes

Reaction equation

[S:1](Cl)(Cl)=[O:2].[C:5]([O:9][C:10](=[O:32])[NH:11][C@:12]([CH2:30][OH:31])([CH3:29])[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:17][CH:16]=1)([CH3:8])([CH3:7])[CH3:6].N1C=CC=CC=1.Cl>C(#N)C.CCOC(C)=O>[C:5]([O:9][C:10]([N:11]1[C:12]([CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:19][CH:20]=2)([CH3:29])[CH2:30][O:31][S@:1]1=[O:2])=[O:32])([CH3:8])([CH3:7])[CH3:6]

Participants

Conditions

Temperature: -10 °C

Procedure

A stirred solution of thionyl chloride (0.14 ml, 1.91 mMol) in acetonitril (10 ml) is cooled to −40° C. At this temperature, a solution of [(R)-3-(4-heptyloxy-phenyl)-1-hydroxymethyl-1-methyl-propyl]-carbamic acid tert-butyl ester (300 mg, 0.76 mMol) in acetonitril (5 ml), and pyridine (0.31 ml, 3.81 mMol) are added successively. The mixture is allowed to warm to −10° C. over 2.5 hours. The reaction mixture is then poured onto a biphasic mixture of AcOEt and HCl (aqueous, 1 M). The aqueous phase is extracted twice with AcOEt. The combined organic layers are washed with NaHCO3 (saturated aqueous solution), dried (Na2SO4) and concentrated under reduced pressure. Column chromatography eluting with 5%→15% AcOEt in heptane gives the title compounds as colourless oils (2 diastereomers, dr=1:1).

Workup

extractionThe aqueous phase is extracted twice with AcOEt
washThe combined organic layers are washed with NaHCO3 (saturated aqueous solution)
dry with materialdried (Na2SO4)
concentrationconcentrated under reduced pressure
washColumn chromatography eluting with 5%→15% AcOEt in heptane

Sources & evidence

ORD record: ord-a5a2fe0492d94de8b066ceb11f7807be
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728020B2

Reaction notes

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