Tetrahydrofuran → HCID 87849764, compound

HRID 1351393Notes

Reaction equation

HRID 1351393 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1)[C:6]([O:8][C@H:9]1[CH2:17][CH2:16][C@@H:15]2[C@@H:11]([CH2:12][N:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]2)[C@@H:10]1[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)=O.[CH2:41]1COCC1>C1(C)C=CC=CC=1.[CH3-].C[Al+]C.[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Cl-].[Ti+3]>[F:39][C:2]([F:40])([F:1])[C:3]1[CH:4]=[C:5]([C:6]([O:8][C@H:9]2[CH2:17][CH2:16][C@@H:15]3[C@@H:11]([CH2:12][N:13]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:14]3)[C@@H:10]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[CH2:41])[CH:32]=[C:33]([C:35]([F:37])([F:38])[F:36])[CH:34]=1

Participants

5

Reactant 2

HCID 8028TetrahydrofuranHCID 87849648HCID 87849648, compound

Product 1

HCID 87849764HCID 87849764, compound

Reagents, catalysts & solvents 2

HCID 53384502mu-Chlorobis(eta5-cyclopentadienyl)(dimethylaluminum)-mu-methylenetitaniumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution 9.5 g (14.0 mmol) of the crude intermediate of step C in dry THF under nitrogen atmosphere at 0° C. was added 66 mL (33 mmol.) of a 0.5 M solution of Tebbe reagent in toluene. The resulting mixture was stirred at 0° C. for 2 hr then carefully quenched by the dropwise addition of 7.5 mL water, then 7.5 mL of 5.0 N aq. NaOH. The resulting suspension was stirred at RT for 0.5 hr and the solids filtered. The resulting filtrate stirred with 5 mL of 5.0 N aq. NaOH for 16 hr and the solids filtered through filter aid. The solvent was evaporated under vacuum and the residue purified by column chromatography eluting with EtOAc/hexanes (1/3) to give the title compound. 1H-NMR (CDCl3): δ: 7.73 (1H, s), 7.55 (2H, s), 7.30–7.18 (2H, m), 7.03 (2H, m), 4.67 (1H, s), 4.37 (1H, s), 4.25 (1H, m), 3.55–3.30(3H, m), 3.27–3.15 (2H, m), 2.81(1H, t, J=12.7 Hz), 2.60 (1H, m), 2.40–30 (2H, m), 1.98 (1H, m), 1.83 (1H, m), 1.55, 1.47 (9H, two singlets)

Workup

  1. customthen carefully quenched by the dropwise addition of 7.5 mL water
  2. stirringThe resulting suspension was stirred at RT for 0.5 hr
  3. filtrationthe solids filtered
  4. stirringThe resulting filtrate stirred with 5 mL of 5.0 N aq. NaOH for 16 hr
  5. filtrationthe solids filtered
  6. filtrationthrough filter aid
  7. customThe solvent was evaporated under vacuum
  8. customthe residue purified by column chromatography
  9. washeluting with EtOAc/hexanes (1/3)

Sources & evidence

ORD record
ord-57f5174bfaba4d9c95c00d97bcc4cd06
Source dataset
uspto-grants-2007_05
Patent number
US07217731B2

Reaction notes

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