2,2,2-Trifluoroethanol → HCID 66833035, compound

HRID 579578Notes

Reaction equation

HRID 579578 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([N:13]1[CH2:17][CH2:16][C@@H:15]([C:18](=O)[CH2:19][CH2:20][CH:21]=[CH2:22])[CH2:14]1)(=[O:12])=[O:11])([O-:3])=[O:2].[C:24]([O-:27])(=O)[CH3:25].[NH4+].FC(F)(F)[CH2:31][OH:32].[C:35]([N+:39]#[C-])([CH3:38])([CH3:37])[CH3:36].[N-:41]=C=O>>[C:24]([NH:41][C:18]([C@@H:15]1[CH2:16][CH2:17][N:13]([S:10]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N+:1]([O-:3])=[O:2])(=[O:12])=[O:11])[CH2:14]1)([CH2:19][CH2:20][CH:21]=[CH2:22])[C:31]([NH:39][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:32])(=[O:27])[CH3:25]

Participants

6

Reactant 5

HCID 64092,2,2-TrifluoroethanolHCID 23577Tert-Butyl isocyanideHCID 105034IsocyanateHCID 517165Ammonium AcetateHCID 66833616HCID 66833616, compound

Product 1

HCID 66833035HCID 66833035, compoundYield 68.4%

Procedure

A solution of (R)-1-(1-(2-nitrophenylsulfonyl)pyrrolidin-3-yl)pent-4-en-1-one (1.03 g, 3.04 mmol) and ammonium acetate (0.548 g, 7.11 mmol) in 2,2,2-trifluoroethanol (1.5 mL, 2.0 mmol) was treated with tert-butyl isocyanide (1.5 mL, 24 mmol) followed by stirring at room temperature. After 8 hours, an additional 0.5 mL of isocyanate was added and the temperature of the reaction was increased to 40° C. After stirring overnight at 40° C., the crude reaction was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was separated, dried over Na2SO4, filtered and concentrated prior to purification of the crude oil by flash column chromatography (silica gel, using 0-100% ethyl acetate in hexanes) to give 2-acetamido-N-tert-butyl-2-((R)-1-(2-nitrophenylsulfonyl)pyrrolidin-3-yl)hex-5-enamide (1.00 g, 68.4%) as a brown foam. 1H NMR (400 MHz, CDCl3, mixture of diastereoisomers) δ 8.07-8.02 (m, 1H), 7.81-7.71 (m, 2H), 7.64-7.59 (m, 1H), 6.85 (2×s, 1H), 5.98-5.63 (br, m, 2H), 5.06-4.95 (m, 2H), 3.61-2.90 (m, 6H), 2.02-2.00 (2×s, 3H), 1.95-1.41 (m, 5H), 1.38-1.36 (2×s, 9H),; ESI MS found for C22H32N4O6S m/z 481.2 (M+H)+; 479.3 (M−H)−.

Workup

  1. temperaturethe temperature of the reaction was increased to 40° C
  2. stirringAfter stirring overnight at 40° C.
  3. customthe crude reaction
  4. customwas partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto purification of the crude oil by flash column chromatography (silica gel, using 0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-cdbb3112b4c44035becdb4ccee32260c
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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