Allyl iodide → (3S,4R,6R)-4-(3-chlorophenyl)-3-(4-chlorophenyl)-6-methyl-2-(2-propanyl)-6-(2-propen-1-yl)-1,2-thiazinan

HRID 1048354Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:13][C@@H:12]([CH3:14])[S:11][N:10]([CH:15]([CH3:17])[CH3:16])[C@@H:9]2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:25](I)[CH:26]=C.[CH3:29][Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:13][C@@:12]([CH3:29])([CH2:14][CH:25]=[CH2:26])[S:11][N:10]([CH:15]([CH3:17])[CH3:16])[C@@H:9]2[C:18]2[CH:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=2)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a degassed solution of 174.7 mg (0.424 mmol) of (3S,4R,6R)-4-(3-chlorophenyl)-3-(4-chlorophenyl)-6-methyl-2-(2-propanyl)-1,2-thiazinan (Example 120, Step A) in THF (1.5 mL) was added allyl iodide (0.55 mL, 6.02 mmol). The resulting solution was heated to 60° C. for 10 minutes, then a 1 M solution of lithium bis(trimethylsilyl)-amide in THF (2.0 mL, 2.00 mmol) was added dropwise, over one minute. After heating at 60° C. for 17 hours, the reaction was cooled to room temperature, quenched with water (2 mL), and then concentrated under reduced pressure. Purification by reverse-phase preparative HPLC using an Agilent Eclipse Plus C18 column (Agilent Technologies, Santa, Clara, Calif.), 0.1% TFA in MeCN/H2O, gradient 40% to 95% over 25 minutes, provided the title compound as a white solid.

Workup

temperatureAfter heating at 60° C. for 17 hours
temperaturethe reaction was cooled to room temperature
customquenched with water (2 mL)
concentrationconcentrated under reduced pressure
customPurification by reverse-phase preparative HPLC
customover 25 minutes

Sources & evidence

ORD record: ord-ac8cc105c17645fab3191e50d3a786f4
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569341B2

Reaction notes

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