Methanol → 6-(2-Thienyl)-2-[3-(2-thienyl)-2-aziridinyl]-3-oxa-1-azabicyclo[3.1.0]hexan-4-ol

HRID 1099019Notes

Reaction equation

HRID 1099019 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[C@H:8]([C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)[NH:7]1)=[O:5])[CH3:2].CC(C[AlH]C[CH:20]([CH3:22])[CH3:21])C.CO.[O-]S([O-])(=O)=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[S:10]1[CH:11]=[CH:12][CH:13]=[C:9]1[CH:8]1[N:7]2[CH:6]1[CH:4]([OH:5])[O:3][CH:1]2[CH:2]1[CH:8]([C:9]2[S:10][CH:22]=[CH:20][CH:21]=2)[NH:7]1

Participants

6

Reactant 4

HCID 887MethanolHCID 14487Diisobutylaluminum hydrideHCID 24436Sodium SulfateHCID 86649086HCID 86649086, compound

Product 1

HCID 250020396-(2-Thienyl)-2-[3-(2-thienyl)-2-aziridinyl]-3-oxa-1-azabicyclo[3.1.0]hexan-4-ol

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-78 °C

Procedure

In a flame dried 100 ml Schlenk tube equipped with a magnetic stirring bar was placed 1c (0.6 g, 3.05 mmol) in 10 ml toluene. The solution was cooled to −78° C. and a 1.5M solution of DIBAL in toluene (4 ml, 6 mmol) was added dropwise along the wall of the vessel. Once the addition was complete, the reaction was allowed to stir at −78° C. for another hour at which point ESI MS showed the lack of starting material. MeOH was slowly added along the wall of the vessel at −78° C. The reaction mixture was then allowed to stir for 30 minutes while warming to room temperature. Saturated Na2SO4 was then added and the solution was allowed to stir for another 15 minutes. The reaction was then filtered and water and ether was added. The organic later was extracted from the partition three times, washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The resulting white solid may be crystallized from EtOAc or MeOH to afford the title compound in 92% (428 mg) yield as a white solid. Silica column chromatography is not recommended. Mp=149-153° C. (decomp.) 1H NMR (CDCl3, 200 MHz) (δ: 7.66 (d, J=11.6 Hz, 1H), 7.23-7.18 (m, 2H), 7.02-6.94 (m, 4H), 5.48 (d, J=11.6 Hz, 1H), 3.27 (dd, J=7.0 Hz, 3.4 Hz, 1H), 2.99 (dd, J=9.0 Hz, 3.4 Hz), 2.90 (d, J=2.6 Hz, 1H), 2.75 (d, J=2.6 Hz, 1H), 1.17 (t, J=6.6 Hz, 1H) ppm. 13C NMR (CDCl3, 75 MHz) δ: 141.5, 121.4, 127.7, 127.3, 125.9, 125.1, 124.8, 124.6, 96.9, 94.4, 54.0, 41.5, 37.5, 32.5 ppm. HRMS (EI) of aldehyde monomer: 152.9561

Workup

  1. customIn a flame dried 100 ml Schlenk tube
  2. customequipped with a magnetic stirring bar
  3. additionOnce the addition
  4. stirringto stir for 30 minutes
  5. temperaturewhile warming to room temperature
  6. stirringto stir for another 15 minutes
  7. filtrationThe reaction was then filtered
  8. additionwater and ether was added
  9. extractionThe organic later was extracted from the
  10. custompartition three times
  11. washwashed with brine
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated under reduced pressure
  14. customThe resulting white solid may be crystallized from EtOAc or MeOH

Sources & evidence

ORD record
ord-20f2f3ed4f5a40f681de68de9ab7001b
Source dataset
uspto-grants-2012_03
Patent number
US08143375B2

Reaction notes

Loading…