Tetrahydrofuran → HCID 18359216, compound

HRID 428787Notes

Reaction equation

HRID 428787 reaction equation
Br[CH2:2][CH2:3][CH:4]1[O:8][CH2:7][CH2:6][O:5]1.[S:9]1[CH:13]=[CH:12][C:11]([C:14]([C:16]2[N:17]=[CH:18][N:19]([C:21]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:20]=2)=[O:15])=[CH:10]1.[CH2:40]1COCC1>CCOC(C)=O>[O:8]1[CH2:7][CH2:6][CH2:40][O:5][CH:4]1[CH2:3][CH2:2][C:14]([C:16]1[N:17]=[CH:18][N:19]([C:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:20]=1)([C:11]1[CH:12]=[CH:13][S:9][CH:10]=1)[OH:15]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 877762-(2-Bromoethyl)-1,3-dioxolaneHCID 12110774HCID 12110774, compound

Product 1

HCID 18359216HCID 18359216, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
30 °C

Procedure

2-(2-Bromoethyl)-1,3-dioxolane (2.9 mL, 25 mmol) was added to Mg (0.7 g, 29 mmol) and THF (50 mL) and heated to 30° C. for 1.5 h under nitrogen atmosphere. A solution of thiophen-3-yl-(1-tritylimidazol-4-yl)methanone (4.69 g, 11.2 mmol) in THF (15 mL) was added slowly and the reaction was heated for 18 h at 30° C. The reaction was diluted with EtOAc, washed with NH4Cl (sat'd), water, and brine. The organic layer was dried with MgSO4, filtered and the solvent was evaporated in vacuo to yield 3-(1,3-dioxan-2-yl)-1-(1-tritylimidazol-4-yl)-1-(thiophen-3-yl)-propan-1-ol as ton crystals (6.01 g, 90%). mp 120-123° C. A solution of this material (1 g, 1.86 mmol) in dichloroethane (10 mL) was added to trimethylsilyl trifluoromethanesulfonate (0.36 mL, 18.6 mmol) and dichloroethane (50 mL) at 0° C. After stirring for 3 h at 25° C. the reaction mixture was cooled to 0° C. and treated with Na2CO3 (sat'd). The organic layer was dried with MgSO4, filtered and solvent was evaporated in vacuo. Purification by chromatography using EtOAc/MeOH/NH4OH, 98:1.9:0.1 as eluant afforded 4-(thionaphth-4-yl)imidazole (0.146 g, 40%). 1H NMR (CD3OD) δ7.31 (t, 1H), 7.40 (s, 1H), 7.60 (d, 1H), 7.61 (d, 1H), 7.77 (d, 1H), 7.80 (s, 1H), 7.83 (d, 1H). This material (0.146 g, 0.73 mmol) was dissolved in hot isopropyl alcohol (4 mL) and treated with maleic acid (0.847 g, 0.73 mmol) to yield Cp-1 (0.23 g, 100%) mp 173-174° C. 1H NMR (DMSO) δ6.12 (s, 2H), 7.45 (t, 1H), 7.68 (d, 1H), 7.88 (d, 1H), 7.90 (d, 1H), 7.92 (s, 1H), 8.05 (d, 1H), 8.62 (s, 1H). MS m/e 201 (M+H), 100.

Workup

  1. temperaturethe reaction was heated for 18 h at 30° C
  2. washwashed with NH4Cl (sat'd), water, and brine
  3. dry with materialThe organic layer was dried with MgSO4
  4. filtrationfiltered
  5. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-3b74b7d4c2fa4687bcc87d9070f21897
Source dataset
uspto-grants-2001_11
Patent number
US06313309B1

Reaction notes

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