Sodium Hydroxide → HCID 69281970, compound

HRID 2362384Notes

Reaction equation

HRID 2362384 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.[Br:17][C:18]1[CH:19]=[N:20][CH:21]=[C:22](/[CH:24]=[CH:25]/[C:26]2[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=2[F:33])[CH:23]=1>C(O)CC.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>[C:4]([O:3][C:1](=[O:8])[NH:2][C@H:24]([C:22]1[CH:21]=[N:20][CH:19]=[C:18]([Br:17])[CH:23]=1)[C@@H:25]([C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[F:33])[OH:12])([CH3:7])([CH3:6])[CH3:5]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 77922tert-Butyl carbamateHCID 521297Tert-Butyl hypochloriteHCID 69085480HCID 69085480, compound

Product 1

HCID 69281970HCID 69281970, compoundYield 134.2%

Reagents, catalysts & solvents 2

HCID 112172021,4-Bis(dihydroquinidine)phthalazineCatalystHCID 10311-PropanolSolvent3×

Procedure

To a solution of tert-butyl carbamate (83 g, 709 mmol) in 1-propanol (780 mL) was added 0.5 M of aqueous sodium hydroxide (1418 mL, 709 mmol), followed by tert-butyl hypochlorite (77 g, 709 mmol) (internal temperature 28.2° C.). The reaction mixture was stirred at ambient temperature for 10 min. To this reaction mixture was added (DHQD)2PHAL (5.52 g, 7.09 mmol) and 1-propanol (780 mL), followed by (E)-3-bromo-5-(2,5-difluorostyryl)pyridine (70.0 g, 236 mmol) and 1-propanol (780 mL). This white mixture was cooled to 0° C. with a methanol/ice bath. Then potassium osmate dihydrate (2.61 g, 7.09 mmol) was added to this mixture. After 30 min of stirring, the ice bath was removed. The reaction was stirred at room temperature overnight. After 16 h, the reaction mixture was partitioned with water (1 L) and EtOAc (2.4 L). The organic layer was washed with 5% sodium sulfite three times (Note: Each wash was mechanically stirred for 10 min to ensure reduction of osmium. The first two washes were dark; the third wash was clear. The organic layer was washed with brine (3×500 mL), dried (sodium sulfate), filtered, and concentrated to give 136 g of crude tert-butyl((1R,2R)-1-(5-bromopyridin-3-yl)-2-(2,5-difluorophenyl)-2-hydroxyethyl)carbamate and tert-butyl((1R,2R)-2-(5-bromopyridin-3-yl)-1-(2,5-difluorophenyl)-2-hydroxyethyl)carbamate (ca. 6:1 ratio). LC/MS (ES+) 430.9 (M+H, 100).

Workup

  1. temperatureThis white mixture was cooled to 0° C. with a methanol/ice bath
  2. stirringAfter 30 min of stirring
  3. customthe ice bath was removed
  4. stirringThe reaction was stirred at room temperature overnight
  5. waitAfter 16 h
  6. customthe reaction mixture was partitioned with water (1 L) and EtOAc (2.4 L)
  7. washThe organic layer was washed with 5% sodium sulfite three times (Note
  8. stirringEach wash was mechanically stirred for 10 min
  9. washthe third wash
  10. washThe organic layer was washed with brine (3×500 mL)
  11. dry with materialdried (sodium sulfate)
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-a624331e28c14e18b0085bc4ce9c7d77
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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