Water → HCID 11161649, compound

HRID 990101Notes

Reaction equation

HRID 990101 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[CH:6]=[CH2:7].CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:38]C)C=C4)N(CC2)C1.S([O-])([O-])=O.[Na+].[Na+].[OH2:81]>CC(O)(C)C>[F:1][C:2]([F:15])([F:16])[C:3]1[CH:4]=[C:5]([C@H:6]([OH:38])[CH2:7][OH:81])[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24437Sodium SulfiteHCID 27732423,5-Bis(trifluoromethyl)styreneHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazine

Product 1

HCID 11161649HCID 11161649, compound

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

3,5-Bis(trifluromethyl)styrene (13 g) was dissolved in a mixture of water (270 ml) and 2-methylpropan-2-ol (270 ml) and cooled to 0° C. AD-mix-α (76 g) was added in one portion and the reaction left to warm to room temperature over 72 hours. The mixture was then cooled to 0° C., sodium sulfite (81 g) added and the reaction mixture extracted into ethyl acetate (3×250 ml). The combined organics were dried (brine, MgSO4) and concentrated under reduced pressure to afford the product as a crude orange solid which was purified on silica eluting with 35% ethyl acetate/iso-hexane to afford the product as a crystalline white solid (chiral hplc, ee 92.2%). This was recrystallised from toluene to give the title compound as a white fibres (chiral hplc, ee 96.2%).

Workup

  1. waitthe reaction left
  2. temperatureto warm to room temperature over 72 hours
  3. temperatureThe mixture was then cooled to 0° C.
  4. extractionthe reaction mixture extracted into ethyl acetate (3×250 ml)
  5. dry with materialThe combined organics were dried (brine, MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customto afford the product as a crude orange solid which
  8. customwas purified on silica eluting with 35% ethyl acetate/iso-hexane

Sources & evidence

ORD record
ord-f865dd4e3b3f4f8f9b9ccf0b089f359a
Source dataset
uspto-grants-2002_10
Patent number
US06458830B1

Reaction notes

Loading…