2,2,2-Trifluoroethanol → (2R,3S)-3-acetamido-2-allyl-N-tert-butyltetrahydrofuran-3-carboxamide

HRID 590693

Reaction equation

HRID 590693 reaction equation
[CH2:1]([CH:4]1[C:8](=O)[CH2:7][CH2:6][O:5]1)[CH:2]=[CH2:3].[C:10]([O-:13])(=O)[CH3:11].[NH4+:14].[C:15]([N+:19]#[C-])([CH3:18])([CH3:17])[CH3:16].FC(F)(F)[CH2:23][OH:24]>O>[C:10]([NH:14][C@@:8]1([C:23]([NH:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:24])[CH2:7][CH2:6][O:5][C@@H:4]1[CH2:1][CH:2]=[CH2:3])(=[O:13])[CH3:11]

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 23577Tert-Butyl isocyanideHCID 517165Ammonium AcetateHCID 136645612-(Prop-2-en-1-yl)oxolan-3-one

Product 1

HCID 67513020(2R,3S)-3-acetamido-2-allyl-N-tert-butyltetrahydrofuran-3-carboxamideYield 36%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 2-allyldihydrofuran-3(2 H)-one (1.2 g, 9.5 mmol) and ammonium acetate (4.39 g, 57.0 mmol) in 2,2,2-trifluoroethanol (5 mL) was treated with tert-butyl isocyanide (2.37 g, 3.23 mL, 28.5 mmol). After stirring at room temperature for 5 days, the reaction mixture diluted with water (50 mL) and extracted using ethyl acetate (2×50 mL). The combined organic layers were washed with saturated aqueous sodium chloride, dried over MgSO4, filtered and concentrated. Purification by flash column chromatography (silica gel, 50% ethyl acetate in methylene chloride) gave (2R3S)-3-acetamido-2-allyl-N-tert-butyltetrahydrofuran-3-carboxamide as a colorless oil (930 mg, 36%) and (2S,3S)-3-acetylamido-2-allyl-N-tert-butyltetrahydrofuran-3-carboxamide as a colorless oil (650 mg, 26%). Analytical data for (2R,3S)-3-acetylamido-2-allyl-N-tert-butyltetrahydrofuran-3-carboxamide: 1H NMR (CDCl3, 300 MHz) δ 6.65 (s, NH, 1 H), 6.06 (s, NH, 1 H), 5.86 (m, 1 H), 5.16 (m, 2 H), 4.20 (dd, J1=9 Hz, J2=4 Hz, 1 H), 3.82 (m, 2 H), 2.54 (m, 2 H), 2.20-2.40 (m, 2 H), 2.03 (s, 3 H), 1.32 (s, 9 H); MS (+CI): m/z for C14H24N2O3: expected 268.2; found 269.2 (M+H)+.

Workup

  1. extractionextracted
  2. washThe combined organic layers were washed with saturated aqueous sodium chloride
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash column chromatography (silica gel, 50% ethyl acetate in methylene chloride)

Sources & evidence

ORD record
ord-7afeff739c6346fc82fd37c13f9455a7
Source dataset
uspto-grants-2016_01
Patent number
US09233985B2

Linked notes

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