Sodium Hydroxide → HCID 86762551, compound

HRID 2207260Notes

Reaction equation

HRID 2207260 reaction equation
[C:1]([NH2:8])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O: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.[CH:75]([C:77]1[CH:88]=[CH:87][C:80]([C:81]([O:83][CH2:84][CH2:85][CH3:86])=[O:82])=[CH:79][CH:78]=1)=[CH2:76]>C(O)CC.O>[C:4]([O:3][C:1]([NH:8][CH:75]([C:77]1[CH:88]=[CH:87][C:80]([C:81]([O:83][CH2:84][CH2:85][CH3:86])=[O:82])=[CH:79][CH:78]=1)[CH2:76][OH:12])=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 77922tert-Butyl carbamateHCID 521297Tert-Butyl hypochloriteHCID 12541502HCID 12541502, compoundHCID 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 86762551HCID 86762551, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 10311-PropanolSolvent3×

Conditions

Temperature
0 °C

Procedure

t-Boc-NH2 (MW 108.57, 9.8 g, 0.0837 mol, 2.95 eq) was dissolved in n-PrOH (110 mL) in a 1 L RB flask, The solution was treated with NaOH (MW 40, 3.6 g, 0.9 mol, 3.17 eq) in H2O (220 mL) and tert-Butyl hypochlorite (MW 108.57, 10 mL, 0.0868 mol, 3.06 eq). After stirring for 20 minutes, the solution was cooled to 0° C. A solution of (DHQ)2phal (MW 779, 0.43 g, 0.552 mmol, 0.019 eq) in n-PrOH (110 mL) was added. A solution of propyl 4-vinylbenzoate (MW 190.24, 5.41 g, 0.0284 mol, 1 eq) in n-PrOH (220 mL) was then added, followed by the addition of K2OsO4 (MW 368.43, 427 mg, 0.00116 mol, 0.04 eq). The reaction mixture was stirred at 0° C. and monitored by LC/MS and TLC. After stirring at 0° C. for 2 hours, the reaction was quenched with sat. Na2SO3 and n-PrOH was removed under vacuum. The residue was diluted with water and extracted with EtOAc (3×). The combined EtOAc fraction was washed with 5% HCl (1×) and brine (1×). After drying over Na2SO4 and filtration, the filtrate was concentrated under vacuum to dryness. The residue was purified on a silica gel column, eluted with EtOAc/Hexanes (10-40%) to give 5.17 g (56% yield) of the pure 1-3. The 1H NMR (DMSO-d6) data is depicted in FIG. 3.

Workup

  1. stirringThe reaction mixture was stirred at 0° C.
  2. stirringAfter stirring at 0° C. for 2 hours
  3. customthe reaction was quenched with sat. Na2SO3 and n-PrOH
  4. customwas removed under vacuum
  5. additionThe residue was diluted with water
  6. extractionextracted with EtOAc (3×)
  7. washThe combined EtOAc fraction was washed with 5% HCl (1×) and brine (1×)
  8. dry with materialAfter drying over Na2SO4 and filtration
  9. concentrationthe filtrate was concentrated under vacuum to dryness
  10. customThe residue was purified on a silica gel column
  11. washeluted with EtOAc/Hexanes (10-40%)
  12. customto give 5.17 g (56% yield) of the pure 1-3

Sources & evidence

ORD record
ord-259409d06870489d9753f2cb4edb4196
Source dataset
uspto-grants-2016_06
Patent number
US09376423B2

Reaction notes

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