Hydrochloric Acid → 5-Bromo-2-[(5S)-5-hydroxymethyl-4,5-dihydroisoxazol-3-yl]pyridine

HRID 459014Notes

Reaction equation

HRID 459014 reaction equation
C([O:6][CH2:7][C@H:8]1[O:12][N:11]=[C:10]([C:13]2[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][N:14]=2)[CH2:9]1)(=O)CCC.[OH-].[Na+].Cl>CO>[Br:19][C:16]1[CH:17]=[CH:18][C:13]([C:10]2[CH2:9][C@@H:8]([CH2:7][OH:6])[O:12][N:11]=2)=[N:14][CH:15]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58822462[(5S)-3-(5-Bromopyridin-2-yl)-4,5-dihydroisoxazol-5-yl]methyl butyrate2×

Product 1

HCID 586537515-Bromo-2-[(5S)-5-hydroxymethyl-4,5-dihydroisoxazol-3-yl]pyridine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

[(5S)-3-(5-Bromopyridin-2-yl)-4,5-dihydroisoxazol-5-yl]methyl butyrate (Intermediate 10, 16.88 g, 0.051 mol) was dissolved in methanol (110 ml). 50% Aqueous sodium hydroxide (3.6 ml, 0.068 mol) was added. The solution was stirred at RT for 15 minutes, 1M HCl (75 ml) was added, followed by concentration in vacuo to ˜100 ml total volume. Water (˜50 ml) was added, and the white precipitate was collected and rinsed with water. The filtrate was extracted twice with ethyl acetate, the organic layers were pooled, dried over sodium sulfate and evaporated. The solid residue was collected and rinsed with 10:1 hexane:ethyl acetate, then combined with the initial precipitate before drying in vacuo to give the title compound as a white crystalline solid, 12.3 g (93%). Chiral HPLC analysis indicated <0.5% of the (−) isomer was present. [α]D=+139 (c=0.01 g/ml in methanol).

Workup

  1. concentrationfollowed by concentration in vacuo to ˜100 ml total volume
  2. additionWater (˜50 ml) was added
  3. customthe white precipitate was collected
  4. washrinsed with water
  5. extractionThe filtrate was extracted twice with ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customThe solid residue was collected
  9. washrinsed with 10:1 hexane
  10. custombefore drying in vacuo

Sources & evidence

ORD record
ord-665fe7c1170c4c6a890fba456bdc4aa6
Source dataset
uspto-grants-2007_03
Patent number
US07192974B2

Reaction notes

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