Sodium Hydroxide → HCID 86673420, compound

HRID 2362373Notes

Reaction equation

HRID 2362373 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]([C:33]([F:36])([F:35])[F:34])=[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]([OH:12])[C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:35])([F:36])[F:34])=[CH:29][CH:28]=2)[C:21]([F:24])=[N:22][CH:23]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 77922tert-Butyl carbamateHCID 521297Tert-Butyl hypochloriteHCID 69083492HCID 69083492, compound

Product 1

HCID 86673420HCID 86673420, compoundYield 101.9%

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 (189 mg, 1.612 mmol) in propanol (7 mL) was added sodium hydroxide (54.1 mg, 1.352 mmol) in water (4 mL) followed by tert-butyl hypochlorite (172 mg, 1.586 mmol) (freshly prepared following an org synthesis prep). After 5 min the solution was cooled to 0° C. and treated with a solution of (DHQD)2PHAL (20.26 mg, 0.026 mmol) in propanol (4 mL). To this solution was added a solution of (E)-5-bromo-2-fluoro-3-(4-(trifluoromethyl)styryl)pyridine (180 mg, 0.520 mmol) in propanol (10 mL). To this solution was added potassium osmate dihydrate (7.66 mg, 0.021 mmol) in one portion. The reaction turned light orange and was allowed to stir at 0° C. overnight allowing the reaction to warm up to room temperature. 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 25% EtOAc/75% Hexanes to 50%/50% EtOAc/Hexanes to afford tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-hydroxy-2-(4-(trifluoromethyl)phenyl)ethylcarbamate (250 mg, 0.530 mmol, 99% yield) as an inseparable mixture with its regioisomer. LC/Mass spec. (Analytical HPLC method 2): RT=2.78 min. Mass=503.07 (MNa)+.

Workup

  1. customfreshly prepared
  2. customan org synthesis prep)
  3. customthe reaction
  4. temperatureto warm up to room temperature
  5. customThe reaction was quenched with a 10% solution of sodium thiosulfate
  6. stirringstirred for 30 min
  7. extractionThe reaction was then extracted with diethylether (3×)
  8. washThe combined organic extracts were combined washed with water
  9. customThe organic layer was separated
  10. dry with materialdried over sodium sulfate
  11. customevaporated in vacuo
  12. customThe crude residue was purified by silica gel chromatography 25% EtOAc/75% Hexanes to 50%/50% EtOAc/Hexanes

Sources & evidence

ORD record
ord-c7b79f156fe04e87859274df1860cac8
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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