Methanesulfonyl chloride → HCID 86670450, compound

HRID 1972699Notes

Reaction equation

[OH:1][CH2:2][C@@H:3]1[N:8]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([OH:24])([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)[CH2:7][CH2:6][N:5]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:4]1.CCN(C(C)C)C(C)C.[CH3:41][S:42](Cl)(=[O:44])=[O:43]>CS(Cl)(=O)=O.CCOC(C)=O>[CH3:41][S:42]([O:1][CH2:2][C@@H:3]1[N:8]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([OH:24])([C:16]([F:17])([F:18])[F:19])[C:20]([F:21])([F:22])[F:23])=[CH:11][CH:10]=2)[CH2:7][CH2:6][N:5]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:4]1)(=[O:44])=[O:43]

Participants

Conditions

Temperature: 0 °C

Procedure

A 150-mL round-bottomed flask was charged with tert-butyl (3R)-3-(hydroxymethyl)-4-(4-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-1-piperazinecarboxylate (0.393 g, 0.857 mmol), DIPEA (0.450 mL, 2.58 mmol) and EtOAc (5 mL). The reaction mixture was cooled to 0° C. and methanesulfonyl chloride (0.095 mL, 1.2 mmol, Sigma-Aldrich, St. Louis, Mo.) was added dropwise. The mixture was stirred at 0° C. for 1 h. At that time, 4 drops of methanesulfonyl chloride was added and stirring at 0° C. resumed for 10 min. The material was directly purified by column chromatography (25 g of silica, 0 to 50% EtOAc in hexanes) to afford tert-butyl (3R)-3-(((methylsulfonyl)oxy)methyl)-4-(4-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-1-piperazinecarboxylate (0.311 g) as a white foam.

Workup

stirringstirring at 0° C.
waitresumed for 10 min
customThe material was directly purified by column chromatography (25 g of silica, 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-de1d0ab0bb224ff98b090608be710819
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431563B2

Reaction notes

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