Sodium Hydroxide → HCID 86673407, compound

HRID 2362336Notes

Reaction equation

HRID 2362336 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:139]=[CH:138][CH:137]=[C:136](/[CH:140]=[CH:141]/[C:142]2[CH:147]=[CH:146][CH:145]=[CH:144][CH:143]=2)[N:135]=1>C(O)CC.O>[Br:133][C:134]1[N:135]=[C:136]([C@@H:140]([NH:2][C:1](=[O:8])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[C@H:141]([OH:12])[C:142]2[CH:143]=[CH:144][CH:145]=[CH:146][CH:147]=2)[CH:137]=[CH:138][CH:139]=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 86673406HCID 86673406, compound

Product 1

HCID 86673407HCID 86673407, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 10311-PropanolSolvent3×

Conditions

Temperature
0 °C

Procedure

To tert-butyl carbamate (2.094 g, 17.88 mmol) in propanol (24 mL) was added sodium hydroxide (0.703 g, 17.59 mmol) in water (45 mL) followed by tert-butyl hypochlorite (1.99 mL, 17.59 mmol). The solution was cooled to 0° C. and treated with a solution of (DHQD)2PHAL (0.112 g, 0.144 mmol) and (DHQ)2PHAL (0.112 g, 0.144 mmol) in propanol (21 mL). The reaction was diluted with propanol (30 ml), and treated with (E)-2-bromo-6-styrylpyridine (1.5 g, 5.77 mmol) as a solid in one portion. To this was added potassium osmate dihydrate (0.085 g, 0.231 mmol) as a solid in one portion. The ice bath was removed and stirring continued for 1.5 h at room temperature. The reaction was placed in a cool bath (ca. 15° C.) and quenched by addition of sodiumthiosulfate (2.1 g) in water (12 mL). The reaction was stirred at room temperature for 30 min. The reaction was diluted with 1:1 diethylether/ethyl acetate, washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (20%-->50% EtOAc/Hex) gave 1.1 g (49%) as a mixture of regioisomers. The reaction was azeotroped with toluene and pumped under high vacuum (2 cycles) to aid in the removal of an unknown impurity. The material was used without additional purification. Mass spec.: 393.1 (MH)+.

Workup

  1. customThe ice bath was removed
  2. customThe reaction was placed in a cool bath
  3. custom(ca. 15° C.) and quenched by addition of sodiumthiosulfate (2.1 g) in water (12 mL)
  4. stirringThe reaction was stirred at room temperature for 30 min
  5. additionThe reaction was diluted with 1:1 diethylether/ethyl acetate
  6. washwashed with water (2×)
  7. dry with materialbrine, dried over magnesium sulfate
  8. concentrationconcentrated
  9. customColumn chromatography (20%-->50% EtOAc/Hex) gave 1.1 g (49%)
  10. additionas a mixture of regioisomers
  11. customThe reaction was azeotroped with toluene
  12. customto aid in the removal of an unknown impurity
  13. customThe material was used without additional purification

Sources & evidence

ORD record
ord-59f7b3444d614f65bca5bb9cc44a17bc
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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