Imidazole → HCID 178455351, compound

HRID 2095671Notes

Reaction equation

HRID 2095671 reaction equation
[I:1][C:2]1[CH:3]=[N:4][N:5]([C@H:7]2[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9][CH2:8]2)[CH:6]=1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].N1C=CN=C1.C(Cl)Cl>CN(C)C1C=CN=CC=1>[Si:14]([O:13][C@H:10]1[CH2:9][CH2:8][C@H:7]([N:5]2[CH:6]=[C:2]([I:1])[CH:3]=[N:4]2)[CH2:12][CH2:11]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 6344DichloromethaneHCID 28928tert-Butyldimethylsilyl chlorideHCID 178521568HCID 178521568, compound

Product 1

HCID 178455351HCID 178455351, compound

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

A mixture of trans-4-(4-iodo-1H-pyrazol-1-yl)cyclohexanol (1.00 g, 3.42 mmol), tert-butyldimethylsilyl chloride (1.03 g, 6.85 mmol), 4-dimethylaminopyridine (80 mg, 0.7 mmol), imidazole (699 mg, 10.3 mmol) and DCM (20 mL, 300 mmol) was stirred rt for 20 min. The material was transferred to a separatory funnel, extracting with DCM and sat. NaHCO3. The organic layer was dry-loaded onto silica gel for column chromatography, eluting with 3% EtOAc/hexanes. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a clear oil. Typical yields are 95%. 1H NMR (400 MHz, DMSO-d6): δ=0.05 (s, 6H), 0.86 (s, 9H), 1.33-1.47 (m, 2H), 1.70-1.91 (m, 4H), 1.96 (d, J=11.9 Hz, 2H), 3.58-3.75 (m, 1H), 4.11-4.21 (m, 1H), 7.49 (s, 1H), 7.92 (s, 1H). MS (ES+): m/z=407.05 (100) [MH+]. HPLC: tR=3.22 min (v.v. non-polar—5 min, ZQ3).

Workup

  1. customThe material was transferred to a separatory funnel
  2. extractionextracting with DCM and sat. NaHCO3
  3. washeluting with 3% EtOAc/hexanes
  4. additionThe fractions containing the pure product
  5. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-561de1891da84623981539b8db2d3645
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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