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

HRID 61349

Reaction equation

HRID 61349 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(2H)-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 (2R 3S)-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-6c33de829c4f4d8b958956cab7162fa8
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Linked notes

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