Dimethylformamide → 1-{[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl}-4-iodo-1H-pyrazole

HRID 2095720Notes

Reaction equation

HRID 2095720 reaction equation
[I:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.CC1C=CC(S(O[CH2:18][C@@H:19]2[CH2:23][O:22][C:21]([CH3:25])([CH3:24])[O:20]2)(=O)=O)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C>>[CH3:24][C:21]1([CH3:25])[O:20][C@H:19]([CH2:18][N:4]2[CH:3]=[C:2]([I:1])[CH:6]=[N:5]2)[CH2:23][O:22]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 770224-IodopyrazoleHCID 2723760(S)-(+)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-Toluenesulfonate

Product 1

HCID 670040911-{[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl}-4-iodo-1H-pyrazole

Conditions

Temperature
100 °C

Procedure

A mixture of 4-iodopyrazole (1.00 g, 5.16 mmol), ((4S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (1.624 g, 5.671 mmol), Cs2CO3 (2.52 g, 7.73 mmol) and DMF (5 mL, 60 mmol) was heated to 100° C. for 2 h. The solution was extracted with EtOAc, and washed with water (2×). The organic layer was concentrated in vacuo and purified via column chromatography, eluting with 2-10% EtOAc/hexanes. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.34 (d, J=8.8 Hz, 6H), 3.76 (dd, J=8.6, 6.1 Hz, 1H), 4.08 (dd, J=8.6, 6.3 Hz, 1H), 4.23-4.37 (m, 2H), 4.39-4.46 (m, 1H), 7.50-7.55 (m, 1H), 7.77 (s, 1H). MS (ES+): m/z=309.01 (100) [MH+]. HPLC: tR=1.34 min (polar—3 min, UPLC-ACQUITY).

Workup

  1. extractionThe solution was extracted with EtOAc
  2. washwashed with water (2×)
  3. concentrationThe organic layer was concentrated in vacuo
  4. custompurified via column chromatography
  5. washeluting with 2-10% EtOAc/hexanes
  6. additionThe fractions containing the pure product
  7. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-413d869858c64ad4b39447b9879d7c2e
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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