tert-Butanol → HCID 67126996, compound

HRID 513996Notes

Reaction equation

HRID 513996 reaction equation
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:22]C)C=C4)N(CC2)C1.[Cl:59][C:60]1[CH:65]=[CH:64][C:63]([C:66]2[C:75]3[C:70](=[CH:71][CH:72]=[CH:73][CH:74]=3)[CH:69]=[C:68](C)[C:67]=2C=C)=[CH:62][CH:61]=1.S([O-])([O-])=O.[Na+].[Na+].[C:85]([OH:89])(C)([CH3:87])[CH3:86]>ClCCl.O>[Cl:59][C:60]1[CH:65]=[CH:64][C:63]([C:66]2[C:75]3[C:70](=[CH:71][CH:72]=[CH:73][CH:74]=3)[CH:69]=[C:68]([CH3:67])[C:86]=2[C@H:85]([OH:89])[CH2:87][OH:22])=[CH:62][CH:61]=1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 24437Sodium SulfiteHCID 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)phthalazineHCID 67126178HCID 67126178, compound

Product 1

HCID 67126996HCID 67126996, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A biphasic mixture of AD-mix-α (4.928 g) in tert-butanol (17.5 mL)/H2O (17.5 mL) was cooled to 0° C. and 1-(4-chlorophenyl)-3-methyl-2-vinyl-naphthalene (3F) (0.980 g, 3.52 mmol) was added. The reaction mixture was stirred for 6 h at 0° C., then stored at −20° C. overnight. The reaction was resumed for 10 h at 0° C., then stored at −20° C. overnight. The reaction was resumed for 8 h at 0° C. until complete. Sodium sulfite (5.3 g) was added at 0° C., then warmed to room temperature and stirred for 30 min to give a white mixture. The mixture was diluted with dichloromethane and H2O. The mixture was extracted with dichloromethane (3×) and the combined organic layer was dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes) to give 3G as a white solid (0.9813 g). 1H-NMR: 300 MHz, (CDCl3) δ 7.72 (d, J=8.1 Hz, 1H), 7.65 (s, 1H), 7.50-7.303 (m, 3H), 7.26-7.07 (m, 4H), 4.92 (dd, J=9.9, 3.6 Hz, 1H), 3.94 (dd, J=10.2, 10.2 Hz, 1H), 3.57 (dd, J=11.1, 3.6 Hz, 1H), 2.69 (s, 3 H).

Workup

  1. waitstored at −20° C. overnight
  2. waitThe reaction was resumed for 10 h at 0° C.
  3. waitstored at −20° C. overnight
  4. waitThe reaction was resumed for 8 h at 0° C.
  5. temperaturewarmed to room temperature
  6. stirringstirred for 30 min
  7. customto give a white mixture
  8. extractionThe mixture was extracted with dichloromethane (3×)
  9. dry with materialthe combined organic layer was dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-47109055f53b40998e88a34a8320fbc8
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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