Imidazole → HCID 59846568, compound

HRID 1363234Notes

Reaction equation

HRID 1363234 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]([NH:5][C@H:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:16])[CH:14]=2)[C@H:9]([OH:17])[CH2:8][CH2:7]1)=[O:4].N1C=CN=C1.[Si:25](Cl)([C:38]([CH3:41])([CH3:40])[CH3:39])([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CN(C=O)C>[Si:25]([O:17][C@H:9]1[C:10]2[C:15](=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[C@H:6]([NH:5][C:3](=[O:4])[C:2]([F:1])([F:18])[F:19])[CH2:7][CH2:8]1)([C:38]([CH3:41])([CH3:40])[CH3:39])([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 59846451HCID 59846451, compound

Product 1

HCID 59846568HCID 59846568, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,2,2-Trifluoro-N-((1R,4R)-7-fluoro-4-hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide (2.71 g, 9.78 mmol, 1 equiv) and imidazole (1.33 g, 19.56 mmol, 2 equiv) were dissolved in anhydrous DMF (40 mL) and cooled in ice bath. Tert-Butyldiphenylsilyl chloride (3.25 mL, 12.71, 1.3 equiv) was added dropwise. The reaction solution was stirred at RT for 16 h. The DMF was removed by evaporation. The residue was dissolved in EtOAc (200 mL) and washed with water, brine and dried (Na2SO4). The organic phase was evaporated to dryness to give an oil residue, which was purified by ISCO (40 g column, EtOAc-hexane 10-50%) to give a white solid product (2.16 g, TLC: pure) and a mixture (3.0 g). 1H NMR (400 MHz, DMSO-d6) δ 9.11 (s, 1H), 7.26-7.30 (q, 1H), 7.09 (m, 1H), 6.98 (dd, 1H), 5.07-5.14 (m, 1H), 4.77-4.80 (m, 1H), 2.06-2.15 (m, 1H), 1.74-1.92 (m, 2H), 1.56-1.669 m, 1H), 1.03 (s, 9H).

Workup

  1. temperaturecooled in ice bath
  2. customThe DMF was removed by evaporation
  3. dissolutionThe residue was dissolved in EtOAc (200 mL)
  4. washwashed with water, brine
  5. dry with materialdried (Na2SO4)
  6. customThe organic phase was evaporated to dryness
  7. customto give an oil residue, which
  8. customwas purified by ISCO (40 g column, EtOAc-hexane 10-50%)
  9. customto give a white solid product (2.16 g, TLC: pure)

Sources & evidence

ORD record
ord-505aefc7ca164c77bf5dc75df954a280
Source dataset
uspto-grants-2011_02
Patent number
US07884109B2

Reaction notes

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