Potassium Carbonate → [6s,9r,11r]2',3',4',5,5',6,7,8,9,10-Decahydro-2-(3-(2-pyridyl)-isoxazol-5-yl)-5'-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole]1',1'-dioxide

HRID 1823965Notes

Reaction equation

HRID 1823965 reaction equation
I[C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH:3]=1.CC1(C)C(C)(C)OB([C:21]2[CH:22]=[CH:23][C:24]3[CH2:31][C@H:30]4[C@:32]5([CH2:36][N:35]([CH2:37][C:38]([F:41])([F:40])[F:39])[S:34](=[O:43])(=[O:42])[NH:33]5)[C@H:27]([CH2:28][CH2:29]4)[CH2:26][C:25]=3[CH:44]=2)O1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.O.C(=O)(O)[O-].[Na+]>[N:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:4]1[CH:3]=[C:2]([C:21]2[CH:22]=[CH:23][C:24]3[CH2:31][C@H:30]4[C@:32]5([CH2:36][N:35]([CH2:37][C:38]([F:41])([F:40])[F:39])[S:34](=[O:42])(=[O:43])[NH:33]5)[C@H:27]([CH2:28][CH2:29]4)[CH2:26][C:25]=3[CH:44]=2)[O:6][N:5]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 111499432-(5-Iodo-3-isoxazolyl)pyridineHCID 23571079[6s,9r,11r]2',3',4',5,5',6,7,8,9,10-Decahydro-2-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-5'-(2,2,2-trifluoroethyl)spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole]1',1'-dioxide

Product 1

HCID 23571075[6s,9r,11r]2',3',4',5,5',6,7,8,9,10-Decahydro-2-(3-(2-pyridyl)-isoxazol-5-yl)-5'-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole]1',1'-dioxideYield 69%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(5-iodoisoxazol-3-yl)pyridine (prepared in the manner of Ku et al Org. Lett. 3 (26), 4185–4187, 2001.) (90 mg, 0.3 mmol), the homochiral boronate from Step 1 (100 mg, 0.2 mmol) potassium carbonate (135 mg, 1 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium (II) dichloromethane complex (5 mg) in toluene (2 mL), ethanol (1 mL) and water (1 mL) was heated under microwave conditions at 100° C. for 5 minutes. More [1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium (II) dichloromethane complex (5 mg) was added and the mixture was again heated under microwave conditions at 100° C. for 5 minutes. The reaction was diluted with sodium bicarbonate (half sat, 20 mL) and extracted with ethylacetate (2×30 mL). The extracts were washed with brine, dried (MgSO4) and evaporated in vacuo to give a brown gum, which was purified by column chromatography, eluting with ethylacetate:iso-hexane (1:4) to give the title compound as a white solid (70 mg, 69%). δ (1H, 400 MHz, CDCl3) 1.32–1.40 (2H, m), 1.74–1.78 (2H, m), 2.48–2.52 (2H, m), 2.74–2.83 (2H, m), 3.26–3.31 (2H, m), 3.46 (2H, s), 3.70 (2H, q, J=8.7 Hz), 4.83 (1H, brs), 7.17 (1H, s), 7.23 (1H, d, J=8.3 Hz), 7.36–7.40 (1H, m), 7.60–7.62 (2H, m), 7.81–7.85 (1H, m), 8.12–8.14 (1H, m), and 8.71–8.72 (1H, m). MS (ES+) 505 ([MH]+).

Workup

  1. customprepared in the manner of Ku et al Org
  2. additionMore [1,1′-bis(diphenylphosphino)ferrocene]dichloro palladium (II) dichloromethane complex (5 mg) was added
  3. extractionextracted with ethylacetate (2×30 mL)
  4. washThe extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customto give a brown gum, which
  8. customwas purified by column chromatography
  9. washeluting with ethylacetate:iso-hexane (1:4)

Sources & evidence

ORD record
ord-a4dac3e0496a4e489f45edc6f98bbf6a
Source dataset
uspto-grants-2006_05
Patent number
US07041689B2

Reaction notes

Loading…