Lithium borohydride → 5-Chloro-n-[4,4,4-trifluoro-1-(hydroxymethyl)-2-(2,2,2-trifluoroethyl)butyl]thiophene-2-sulfonamide

HRID 1985971Notes

Reaction equation

HRID 1985971 reaction equation
[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][CH:11]([C:23](OC)=[O:24])[CH:12]([CH2:18][C:19]([F:22])([F:21])[F:20])[CH2:13][C:14]([F:17])([F:16])[F:15])(=[O:9])=[O:8])=[CH:4][CH:3]=1.[Li+].[BH4-]>C1COCC1>[Cl:1][C:2]1[S:6][C:5]([S:7]([NH:10][CH:11]([CH2:23][OH:24])[CH:12]([CH2:18][C:19]([F:20])([F:22])[F:21])[CH2:13][C:14]([F:16])([F:15])[F:17])(=[O:8])=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 86594495methyl N-[(5-chlorothien-2-yl)sulfonyl]-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-dl-norvalinate

Product 1

HCID 114300705-Chloro-n-[4,4,4-trifluoro-1-(hydroxymethyl)-2-(2,2,2-trifluoroethyl)butyl]thiophene-2-sulfonamideYield 2.36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of methyl N-[(5-chlorothien-2-yl)sulfonyl]-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-dl-norvalinate (0.5 g, 1.11 mmol) in THF (10 mL) was added LiBH4 (2.28 mL, 4.46 mmol) under N2 atmosphere at 0° C. The reaction was allowed to warm to 25° C. for 19 h. The reaction was cooled to 0° C. and quenched with 2N HCl (slow addition), diluted in ether (40 mL) and the organic layer washed sequentially with 1N aqueous HCl (10 mL), saturated aqueous NaHCO3 (10 mL) and brine (15 mL), then dried over MgSO4, filtered and concentrated to obtain a crude oil (0.362 g). The crude product was purified by the Biotage Flash™ 12 chromatography system, eluent: 1:6 EtOAc-hexanes, to afford 5-chloro-N-[4,4,4-trifluoro-1-(hydroxymethyl)-2-(2,2,2-trifluoroethyl)butyl]thiophene-2-sulfonamide as a colorless oil (0.001 g, 2.36%). Mass Spectrum (−ESI): 418 (M−H)−.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customquenched with 2N HCl (slow addition)
  3. additiondiluted in ether (40 mL)
  4. washthe organic layer washed sequentially with 1N aqueous HCl (10 mL), saturated aqueous NaHCO3 (10 mL) and brine (15 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto obtain a crude oil (0.362 g)
  9. customThe crude product was purified by the Biotage Flash™ 12 chromatography system, eluent

Sources & evidence

ORD record
ord-c98acfb62300461bb6323d476e415c6f
Source dataset
uspto-grants-2009_06
Patent number
US07547725B2

Reaction notes

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