Sodium Hydroxide → HCID 70957274, compound

HRID 2362356Notes

Reaction equation

HRID 2362356 reaction equation
[C:1](=[O:8])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[NH2:2].[OH-].[Na+].Cl[O:12]C(C)(C)C.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.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.[Br:133][C:134]1[CH:135]=[C:136]([CH:145]=[CH:146][CH:147]=1)/[CH:137]=[CH:138]/[C:139]1[CH:140]=[N:141][CH:142]=[CH:143][CH:144]=1>C(O)CC.O>[Br:133][C:134]1[CH:135]=[C:136]([C@@H:137]([NH:2][C:1](=[O:8])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[C@H:138]([OH:12])[C:139]2[CH:140]=[N:141][CH:142]=[CH:143][CH:144]=2)[CH:145]=[CH:146][CH:147]=1

Participants

9

Reactant 6

HCID 14798Sodium HydroxideHCID 77922tert-Butyl carbamateHCID 521297Tert-Butyl hypochloriteHCID 112172021,4-Bis(dihydroquinidine)phthalazineHCID 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 69086206HCID 69086206, compound

Product 1

HCID 70957274HCID 70957274, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 10311-PropanolSolvent3×

Conditions

Temperature
0 °C

Procedure

To tert-butyl carbamate (1256 mg, 10.73 mmol) in propanol (25 mL) was added sodium hydroxide (422 mg, 10.55 mmol) in water (30 mL) followed by tert-butyl hypochlorite (1.191 mL, 10.55 mmol). The solution was cooled to 0° C. and (DHQD)2PHAL (67.4 mg, 0.086 mmol) and (DHQ)2PHAL (67.4 mg, 0.086 mmol) were added in propanol (20 mL) followed by (E)-3-(3-bromostyryl)pyridine (900 mg, 3.46 mmol) in propanol (25 mL) and finally potassium osmate dihydrate (51.0 mg, 0.138 mmol) in one portion. The mixture was allowed to stir overnight and come to ambient temperature in the process. The mixture was quenched with sodium sulfite (50 mL) and the mixture was extracted with 3×50 mL ethyl acetate and the combined organics were washed with sodium sulfite (25 mL) and brine (25 mL), dried over MgSO4, filtered and concentrated to an amber oil which was loaded with dichloromethane onto a 90 g silica gel cartridge pre-equilibrated with 5% ethyl acetate/hexanes. Elution with 5 to 100% ethyl acetate over 2.5 L provided 965 mg (71%) as a mixture of regioisomers. LC/MS (analytical HPLC method 1; 1.63 min): Anal. Calcd. for [M+H]+ C18H21BrN2O3: 393.07. found 392.97.

Workup

  1. customcome to ambient temperature in the process
  2. customThe mixture was quenched with sodium sulfite (50 mL)
  3. extractionthe mixture was extracted with 3×50 mL ethyl acetate
  4. washthe combined organics were washed with sodium sulfite (25 mL) and brine (25 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to an amber oil which
  8. washElution with 5 to 100% ethyl acetate over 2.5 L
  9. customprovided 965 mg (71%)
  10. additionas a mixture of regioisomers
  11. customLC/MS (analytical HPLC method 1; 1.63 min)

Sources & evidence

ORD record
ord-c92f8a903c4b48f6980b59418d231817
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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