Sodium Hydroxide → HCID 70958312, compound

HRID 2362367Notes

Reaction equation

HRID 2362367 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]=[C:20](/[CH:25]=[CH:26]/[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[C:21]([F:24])=[N:22][CH:23]=1>C(O)CC.O.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:17][C:18]1[CH:19]=[C:20]([C@@H:25]([NH:2][C:1](=[O:8])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[C@@H:26]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[OH:12])[C:21]([F:24])=[N:22][CH:23]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 77922tert-Butyl carbamateHCID 521297Tert-Butyl hypochloriteHCID 69082787HCID 69082787, compound

Product 1

HCID 70958312HCID 70958312, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 112172021,4-Bis(dihydroquinidine)phthalazineCatalystHCID 962WaterSolventHCID 10311-PropanolSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl carbamate (1431 mg, 12.22 mmol) in propanol (10 mL) was added sodium hydroxide (481 mg, 12.02 mmol) in water (4 mL) followed by tert-butyl hypochlorite (1305 mg, 12.02 mmol). After 5 min the solution was cooled to 0° C. and treated with a solution of (DHQD)2PHAL (154 mg, 0.197 mmol) in propanol (4 mL). To this solution was added a solution of (E)-5-bromo-2-fluoro-3-(4-fluorostyryl)pyridine (1167 mg, 3.94 mmol) in propanol (10 mL). To this solution was added potassium osmate dihydrate (58.1 mg, 0.158 mmol) in one portion. The reaction turned light orange and was allowed to stir at 0° C. for 1 hr. The ice bath was then removed and the reaction was allowed to warm to room temperature and stirred over night. The reaction was quenched with a 10% solution of sodium thiosulfate and stirred for 30 min. The reaction was then extracted with diethylether (3×). The combined organic extracts were combined washed with water, then brine. The organic layer was separated, dried over sodium sulfate and evaporated in vacuo. The crude residue was purified by silica gel chromatography 5% acetone/95% Hexanes to 50%/50% Acetone/Hexanes to afford tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-(4-fluorophenyl)-2-hydroxyethylcarbamate (1450 mg, 3.38 mmol, 86% yield) along with its regioisomer as an inseparable mixture. LC/Mass spec. (Analytical HPLC method 2): RT=2.07 min. Mass=429.30 (MH)+.

Workup

  1. customThe ice bath was then removed
  2. temperatureto warm to room temperature
  3. stirringstirred over night
  4. customThe reaction was quenched with a 10% solution of sodium thiosulfate
  5. stirringstirred for 30 min
  6. extractionThe reaction was then extracted with diethylether (3×)
  7. washThe combined organic extracts were combined washed with water
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulfate
  10. customevaporated in vacuo
  11. customThe crude residue was purified by silica gel chromatography 5% acetone/95% Hexanes to 50%/50% Acetone/Hexanes

Sources & evidence

ORD record
ord-04f97906daad4bb2b40b34934c45555a
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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