4-Methylpyrazole → ethyl (2R)-2-methyl-4-(4-methyl-1H-pyrazol-1-yl)-2-(methylsulfonyl)butanoate

HRID 2405923Notes

Reaction equation

[CH3:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.Br[CH2:8][CH2:9][C@@:10]([CH3:20])([S:16]([CH3:19])(=[O:18])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12].C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.CCOC(C)=O>[CH3:20][C@@:10]([S:16]([CH3:19])(=[O:17])=[O:18])([CH2:9][CH2:8][N:4]1[CH:3]=[C:2]([CH3:1])[CH:6]=[N:5]1)[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of the 4-methylpyrazole (143 mg, 1.74 mmol, 1 eq) and (R)-ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate (500 mg 1.74 mmol, 1 eq) in THF (10 mL) was added cesium carbonate (2.27 g, 6.96 mmol, 4 eq). The resulting suspension was heated to 55° C. and allowed to stir overnight. The reaction was then diluted with EtOAc (10 mL) and the mixture filtered through a pad of celite, which was eluted with ˜10 mL of EtOAc. The crude material was purified by flash chromatography on a 40 g silica gel column eluting with an heptane/ethyl acetate/MeOH gradient) to give ethyl (2R)-2-methyl-4-(4-methyl-1H-pyrazol-1-yl)-2-(methylsulfonyl)butanoate which was used directly in the next step. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.27 (s, 1H), 7.13 (s, 1H), 4.30-4.11 (m, 2H), 3.03 (s, 3H), 2.80-2.71 (m, 1H), 2.51-2.41 (m, 1H), 2.04 (s, 3H), 1.66 (s, 3H). LC-MS M+H+289.4.

Workup

filtrationthe mixture filtered through a pad of celite, which
washwas eluted with ˜10 mL of EtOAc
customThe crude material was purified by flash chromatography on a 40 g silica gel column
washeluting with an heptane/ethyl acetate/MeOH gradient)

Sources & evidence

ORD record: ord-20a474de14394c429d7e616b99ef549f
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809333B2

Reaction notes

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