Toluene → [3-(3,5-Dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methanol

HRID 2423475Notes

Reaction equation

HRID 2423475 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:19])[C:7]=1[C:8]1[C:12]([C:13](O)=[O:14])=[C:11]([CH:16]([CH3:18])[CH3:17])[O:10][N:9]=1.C(N(CC)CC)C.C(OC(Cl)=O)(C)C.C1(C)C=CC=CC=1.[BH4-].[Na+]>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:19])[C:7]=1[C:8]1[C:12]([CH2:13][OH:14])=[C:11]([CH:16]([CH3:17])[CH3:18])[O:10][N:9]=1

Participants

8

Reactant 5

HCID 1140TolueneHCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 597090383-(3,5-Dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolecarboxylic acid

Product 1

HCID 59709040[3-(3,5-Dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methanolYield 61.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-(3,5-dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolecarboxylic acid (0.54 g, 1.8 mmol) in THF (9 mL), was stirred as triethylamine (0.25 mL, 1.8 mmol) was added. The solution was cooled in ice bath before the addition of a 1 N solution of isopropylchloroformate in toluene (1.8 mL, 1.8 mmol). The solution was allowed to stir for 30 minutes before being filtered into a solution of sodium borohydride (91 mg, 2.4 mmol) in water (0.62 mL). The mixture was allowed to warm to room temperature and stir for 3 days. The mixture was filtered and the filtrate was partitioned between brine and ethyl acetate. The organic layer was dried with MgSO4, filtered and concentrated. The residue was purified by chromatography (silica gel, hexane to 2:3 ethyl acetate:hexanes) to provide [3-(3,5-dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methanol (0.32 g, 57% as 0.3 ethyl acetate). 1H NMR (400 MHz, DMSO-d6): δ 8.79 (s, 2H), 4.96 (t, J=5 Hz, 1H), 4.20 (d, J=5 Hz, 2H), 3.35 (septet, J=7 Hz, 1H), 1.29 (d, J=7 Hz, 6H).

Workup

  1. additionwas added
  2. temperatureThe solution was cooled in ice bath
  3. stirringstir for 3 days
  4. filtrationThe mixture was filtered
  5. customthe filtrate was partitioned between brine and ethyl acetate
  6. dry with materialThe organic layer was dried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography (silica gel, hexane to 2:3 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-d9801ef5d5574ad3bb84d6f690bf61c1
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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