Diisobutylaluminumhydride → {5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-methanol

HRID 2045946Notes

Reaction equation

HRID 2045946 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.C([O:13][C:14]([C:16]1[S:17][C:18]([C:22]2[CH2:26][C:25]([C:31]3[CH:36]=[C:35]([Cl:37])[CH:34]=[C:33]([Cl:38])[CH:32]=3)([C:27]([F:30])([F:29])[F:28])[O:24][N:23]=2)=[CH:19][C:20]=1[CH3:21])=O)C>C(OCC)C>[Cl:38][C:33]1[CH:32]=[C:31]([C:25]2([C:27]([F:28])([F:30])[F:29])[O:24][N:23]=[C:22]([C:18]3[S:17][C:16]([CH2:14][OH:13])=[C:20]([CH3:21])[CH:19]=3)[CH2:26]2)[CH:36]=[C:35]([Cl:37])[CH:34]=1

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 665872885-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid ethyl ester

Product 1

HCID 66587355{5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-methanolYield 79.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Diisobutylaluminium hydride (DIBAL-H, 28.4 ml, 1M in Toluene) is added to a solution of 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid ethyl ester (6.42 g) in diethyl ether (120 ml) under nitrogen at −5° C. After 15 min at −5° C., the cold bad is removed. After 3 hours at room temperature, the reaction mixture is diluted with ethyl acetate and is quenched with a saturated solution of NaHCO3. The organic phase is separated and the aqueous phase is extracted once with ethyl acetate. The combined organic phases are extracted with a saturated solution of NaHCO3 and with a saturated aqueous solution of NaCl, dried over Na2SO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield {5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-yl}-methanol (4.63 g) as a light yellow foam. MS (HPLC/MS): 410 (MH+). Retention time: 1.90 min.

Workup

  1. customthe cold bad is removed
  2. waitAfter 3 hours at room temperature
  3. additionthe reaction mixture is diluted with ethyl acetate
  4. customis quenched with a saturated solution of NaHCO3
  5. customThe organic phase is separated
  6. extractionthe aqueous phase is extracted once with ethyl acetate
  7. extractionThe combined organic phases are extracted with a saturated solution of NaHCO3 and with a saturated aqueous solution of NaCl
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-10fc1b05b9d348919bfb39be832fe05e
Source dataset
uspto-grants-2013_11
Patent number
US08592418B2

Reaction notes

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