Sodium Hydroxide → 5-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydroisoxazole-3-carboxylic acid

HRID 1643518Notes

Reaction equation

HRID 1643518 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]([CH:9]1[O:13][N:12]=[C:11]([C:14]([O:16]CC)=[O:15])[CH2:10]1)([OH:8])[C:4]([F:7])([F:6])[F:5].[OH-].[Na+]>C(O)C>[F:7][C:4]([F:5])([F:6])[C:3]([CH:9]1[O:13][N:12]=[C:11]([C:14]([OH:16])=[O:15])[CH2:10]1)([OH:8])[C:2]([F:20])([F:19])[F:1]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 11266840Ethyl 5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-4,5-dihydroisoxazole-3-carboxylate

Product 1

HCID 113234795-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)-4,5-dihydroisoxazole-3-carboxylic acidYield 98.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]-4,5-dihydroisoxazole-3-carboxylate from example 8-1 (2.58 g, 8.34 mmol) in ethanol (5 ml) was added 1 N NaOH (16.7 mL). The mixture was stirred at r.t. for 1 h. Ethanol was removed under reduced pressure, and to the aqueous solution was added concentrated HCl (1.5 mL). The product was extracted 3 times with EtOAc and 2 times with isopropyl ether, and the combined organic layers were dried over MgSO4. Solvents were removed under reduced pressure to afford the carboxylic acid intermediate as an off-white solid (2.30 g, 98%). 1H NMR (DMSO-d6) δ 3.2-3.4 (m, 2H), 5.12 (t, 3H), 8.6 (br, 1H); ESIMS: m/z 280 (M−H).

Workup

  1. customEthanol was removed under reduced pressure
  2. additionto the aqueous solution was added concentrated HCl (1.5 mL)
  3. extractionThe product was extracted 3 times with EtOAc and 2 times with isopropyl ether
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. customSolvents were removed under reduced pressure

Sources & evidence

ORD record
ord-117e75f9519f495d86f0fe80f2599563
Source dataset
uspto-grants-2012_02
Patent number
US08119819B2

Reaction notes

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