Sodium Hydroxide → tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-(2,5-difluorophenyl)-2-hydroxyethylcarbamate

HRID 2362414Notes

Reaction equation

HRID 2362414 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.[Br:75][C:76]1[CH:77]=[C:78](/[CH:83]=[CH:84]/[C:85]2[CH:90]=[C:89]([F:91])[CH:88]=[CH:87][C:86]=2[F:92])[C:79]([F:82])=[N:80][CH:81]=1>C(O)CC.O>[Br:75][C:76]1[CH:77]=[C:78]([C@@H:83]([NH:2][C:1](=[O:8])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[C@@H:84]([C:85]2[CH:90]=[C:89]([F:91])[CH:88]=[CH:87][C:86]=2[F:92])[OH:12])[C:79]([F:82])=[N:80][CH:81]=1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 77922tert-Butyl carbamateHCID 521297Tert-Butyl hypochloriteHCID 112172021,4-Bis(dihydroquinidine)phthalazineHCID 69084839(E)-5-Bromo-3-(2,5-difluorostyryl)-2-fluoropyridine

Product 1

HCID 69281853tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-(2,5-difluorophenyl)-2-hydroxyethylcarbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 10311-PropanolSolvent3×

Conditions

Temperature
0 °C

Procedure

To tert-butyl carbamate (0.462 g, 3.95 mmol) in propanol (6 mL) was added sodium hydroxide (0.155 g, 3.88 mmol) in water (12 mL) followed by tert-butyl hypochlorite (0.438 mL, 3.88 mmol). The solution was cooled to 0° C., and (DHQD)2PHAL (0.060 g, 0.076 mmol) was added in propanol (6 mL), followed by (E)-5-bromo-3-(2,5-difluorostyryl)-2-fluoropyridine (0.4 g, 1.273 mmol) as a solid. The remaining residue was dissolved in propanol (12 mL) and added to the reaction mixture to give a suspension. To this was added potassium osmate dihydrate (0.019 g, 0.051 mmol) as a solid in one portion. The reaction was allowed to gradually warm in the dewar overnight. The reaction was recooled to 0° C., and the reaction quenched by addition of sodium thiosulfate (0.5 g) in water (3 mL). The ice bath was removed, and the reaction stirred at room temperature for 30 min. The reaction was diluted with diethyl ether, washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25% EtOAc/Hex) gave 0.445 g (78%) as a white foam solid. Mass spec.: 447.1 (MH)+.

Workup

  1. additionadded to the reaction mixture
  2. customto give a suspension
  3. temperatureto gradually warm in the dewar overnight
  4. customwas recooled to 0° C.
  5. customthe reaction quenched by addition of sodium thiosulfate (0.5 g) in water (3 mL)
  6. customThe ice bath was removed
  7. additionThe reaction was diluted with diethyl ether
  8. washwashed with water (2×)
  9. dry with materialbrine, dried over magnesium sulfate
  10. concentrationconcentrated
  11. customColumn chromatography (25% EtOAc/Hex) gave 0.445 g (78%) as a white foam solid

Sources & evidence

ORD record
ord-d133e0e1d1ba430eb64ab91a8f05c3c3
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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