Methanesulfonyl chloride → (R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride

HRID 534112Notes

Reaction equation

[OH:1][N:2]=[C:3]([Cl:14])[C@H:4]1[CH2:8][O:7][C:6]2([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[O:5]1.[CH3:15][S:16](Cl)(=[O:18])=[O:17].C(N(C(C)C)C(C)C)C>C1COCC1>[CH3:15][S:16]([O:1][N:2]=[C:3]([Cl:14])[C@H:4]1[CH2:8][O:7][C:6]2([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[O:5]1)(=[O:18])=[O:17]

Participants

Conditions

Temperature: 3 °C

Procedure

To a 4 neck 5 L flask was added (R)-N-hydroxy-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (158 g, 719 mmol) in 2.5 L of THF. The mixture was cooled to 3° C. and methanesulfonyl chloride (56.1 ml, 719 mmol) added in 10 ml portions over 10 minutes. N-ethyl-N-isopropylpropan-2-amine (126 ml, 719 mmol) was added through an addition funnel over 12 minutes. The reaction was stirred in an ice bath for 30 minutes and then at ambient temperature for 1 hour. The reaction was filtered and the solids were washed with MTBE (about 3 L). The filtrate was concentrated and the residue was purified by chromatography (3 kg silica, 7:1 to 3:1 Hexane/EtOAc) to afford an oil that slowly solidified under vacuum. The solids were ground using a mortar and pestle, washed with hexanes (about 1000 mL) and dried to afford (R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (158 g, 531 mmol, 73.8% yield) as a white solid.

Workup

waitat ambient temperature for 1 hour
filtrationThe reaction was filtered
washthe solids were washed with MTBE (about 3 L)
concentrationThe filtrate was concentrated
customthe residue was purified by chromatography (3 kg silica, 7:1 to 3:1 Hexane/EtOAc)
customto afford an oil that
washwashed with hexanes (about 1000 mL)
customdried

Sources & evidence

ORD record: ord-b3cdcc06feb1499baeb5396f6f0ca5a3
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853409B2

Reaction notes

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