Water → HCID 117678172, compound

HRID 920128Notes

Reaction equation

HRID 920128 reaction equation
[F:1][C:2]1[C:3]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6](/[CH:8]=[CH:9]/[CH3:10])[CH:7]=1.CS(N)(=O)=[O:26].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(OC)C=C4)N(CC2)C1.S([O-])([O-])=O.[Na+].[Na+].[OH2:93]>C(O)(C)(C)C.CCOC(C)=O>[OH:93][C@@H:8]([C:6]1[CH:7]=[C:2]([F:1])[C:3]([N:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:15][CH2:16]2)=[N:4][CH:5]=1)[C@@H:9]([OH:26])[CH3:10]

Participants

8

Reactant 5

HCID 962WaterHCID 24437Sodium SulfiteHCID 72879MethanesulfonamideHCID 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 71165119HCID 71165119, compound

Product 1

HCID 117678172HCID 117678172, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 105 (2.67 g, 8.29 mmol) in tert-butanol (80 mL) and water (80 mL) was added methanesulfonamide (0.79 g, 8.29 mmol, Sigma-Aldrich). The mixture was cooled to 5° C. and AD-mix-α (11.50 g, 8.29 mmol) was added to form a reaction mixture. After warming the reaction mixture to a temperature of about 25° C. and stirring for 16 hours, excess solid sodium sulfite was added and the resulting slurry was allowed to stir at 15° C. for 30 min. The mixture was extracted twice with EtOAc. The organic portions were combined, washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was chromatographed on a silica gel column eluted with 50:50 EtOAc:hexanes and 70:30 EtOAc:hexanes to provide 106 as a solid (>99% yield).

Workup

  1. customto form a reaction mixture
  2. temperatureAfter warming the reaction mixture to a temperature of about 25° C.
  3. stirringto stir at 15° C. for 30 min
  4. extractionThe mixture was extracted twice with EtOAc
  5. washwashed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was chromatographed on a silica gel column
  9. washeluted with 50:50 EtOAc

Sources & evidence

ORD record
ord-b6e2d1e1dd7442fc9cdd43b8ac327bb5
Source dataset
uspto-grants-2016_03
Patent number
US09273043B2

Reaction notes

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