Diethyl Ether → HCID 90042055, compound

HRID 929209Notes

Reaction equation

HRID 929209 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:22][C:21]([O:23][C@@H:24]3[CH2:28][O:27][C@@H:26]4[C:29](=[O:32])[CH2:30][O:31][C@H:25]34)=[N:20][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:9]=1.[CH2:33]([Mg]Br)[CH:34]=[CH2:35].CCOCC>C1COCC1>[CH2:35]([C@:29]1([OH:32])[C@H:26]2[O:27][CH2:28][C@@H:24]([O:23][C:21]3[NH:22][C:4]4[C:5]([N:20]=3)=[N:6][C:7]([C:8]3[CH:13]=[CH:12][C:11]([C:14]5[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=5)=[CH:10][CH:9]=3)=[C:2]([Cl:1])[CH:3]=4)[C@H:25]2[O:31][CH2:30]1)[CH:34]=[CH2:33]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 90041963HCID 90041963, compoundHCID 178455850HCID 178455850, compound

Product 1

HCID 90042055HCID 90042055, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A stirred suspension of (3R,3aR,6aS)-3-[[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,6a-tetrahydrofuro[3,2-b]furan-6-one (314.3 mg, 0.702 mmol) in THF (7.0 ml) was degassed (3×) and placed under nitrogen after being cooled to 0° C. in an ice bath. Allylmagnesium bromide 1.0 M in ether (1.4 ml, 1.400 mmol) was added to the reaction mixture dropwise over 6 minutes. After 1 hour, the reaction mixture was removed from the ice bath and allowed to warm to room temperature. The reaction mixture was transferred via pipette into saturated aqueous NaHCO3 (50 ml) before being partitioned between EtOAc (100 ml) and water (50 ml). The aqueous layer was extracted with EtOAc (2×50 ml). The organic layers were combined, washed with brine (1×30 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to give a pale yellow residue. The residue was purified by flash chromatography utilizing a 40 g silica RediSep Rf® column and employing a 0-80% EtOAc/hexane gradient. The product fractions were combined and evaporated under reduced pressure to give the title compound as a colorless residue. LC-MS: calculated for C27H24ClN3O4 489.15 observed m/e: 490.19 (M+H)+ (Rt 1.23/2 min); 1H NMR δ (ppm) (CD3OD): 7.81 (s, 1H), 7.70-7-75 (m, 4H), 7.69 (d, J=7.9 Hz, 2H), 7.47 (t, J=7.7 Hz, 2H), 7.36 (t, J=7.4 Hz, 1H), 5.90-5.99 (m, 1H), 5.53 (qt, J=5.5 Hz, J=10.8 Hz, 1H), 5.14 (broad d, J=12.9 Hz, 2H), 4.96 (t, J=5.3 Hz, 1H), 4.10-4.18 (m, 3H), 3.67 (abqt, J=8.5 Hz, J=24.6 Hz, 2H), 2.30-2.38 (m, 2H).

Workup

  1. customwas degassed (3×)
  2. customthe reaction mixture was removed from the ice bath
  3. temperatureto warm to room temperature
  4. custombefore being partitioned between EtOAc (100 ml) and water (50 ml)
  5. extractionThe aqueous layer was extracted with EtOAc (2×50 ml)
  6. washwashed with brine (1×30 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customto give a pale yellow residue
  11. customThe residue was purified by flash chromatography
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-38b39793f7a34437b464202c17f88bc3
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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