Dichloromethane → HCID 66833616, compound

HRID 579577Notes

Reaction equation

HRID 579577 reaction equation
[C:1]([C@@H:7]1[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8]1)(=[O:6])[CH2:2][CH2:3][CH:4]=[CH2:5].C(Cl)Cl.FC(F)(F)C(O)=O.C(N(CC)CC)C.[N+:36]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[S:45](Cl)(=[O:47])=[O:46])([O-:38])=[O:37]>C(=O)(O)[O-].[Na+]>[N+:36]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[S:45]([N:9]1[CH2:10][CH2:11][C@@H:7]([C:1](=[O:6])[CH2:2][CH2:3][CH:4]=[CH2:5])[CH2:8]1)(=[O:47])=[O:46])([O-:38])=[O:37]

Participants

7

Reactant 5

HCID 6344Dichloromethane2×HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 155402-Nitrobenzenesulfonyl chlorideHCID 66833274HCID 66833274, compound

Product 1

HCID 66833616HCID 66833616, compoundYield 90.1%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-tert-butyl 3-pent-4-enoylpyrrolidine-1-carboxylate (300 mg, 1 mmol) in methylene chloride (5 mL, 80 mmol) was added trifluoroacetic acid (2 mL, 20 mmol) and the resultant mixture was stirred at room temperature for 1 h. The crude reaction mixture was then concentrated to obtain a crude oil which was re-dissolved in methylene chloride (5 mL, 80 mmol) prior to the addition of triethylamine (1 mL, 7 mmol). This solution was cooled to 0° C. before adding 2-nitrobenzenesulfonyl chloride (450 mg, 2.0 mmol) in a single portion. The reaction mixture, which immediately turned blue in color, was stirred overnight at room temperature. At the end of the reaction, the solution was diluted with saturated aqueous sodium bicarbonate (50 mL) to give two layers which were separated. The aqueous layer was further extracted with methylene chloride (2×20 mL) and the combined organic layers were dried over Na2SO4, filtered and concentrated to give a blue oil, which was purified by flash column chromatography (silica gel, eluting with 0-100% ethyl acetate in hexanes) to give (R)-1-(1-(2-nitrophenylsulfonyl)pyrrolidin-3-yl)pent-4-en-1-one (305 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 8.07-8.03 (m, 1H), 7.76-7.70 (m, 2H), 7.66-7.62 (m, 1H), 5.78 (ddt, J1=17.0 Hz, J2=10.4 Hz, J3=6.5 Hz, 1H), 5.07-4.97 (m, 2H), 3.70 (dd, J1=12.0 Hz, J2=8.0 Hz, 1H) 3.61 (dd, J1=12.0 Hz, J2=8.1 Hz, 1H), 3.52 (t, J=8.1 Hz, 2H), 3.24 (p, J=8.0 Hz, 1H), 2.59 (td, J1=7.3 Hz, J2=3.6 Hz, 2H), 2.32 (q, J=6.8 Hz, 2H), 2.24-2.16 (m, 1H), 2.14-2.05 (m, 1H), 1.28 (ddd, J1=17.8 Hz, J2=10.6 Hz, J3=7.3 Hz, 1H); ESI MS found for C15H18N2O5S m/z 339.3 (M+H)+.

Workup

  1. customThe crude reaction mixture
  2. concentrationwas then concentrated
  3. customto obtain a crude oil which
  4. customAt the end of the reaction
  5. customto give two layers which
  6. customwere separated
  7. extractionThe aqueous layer was further extracted with methylene chloride (2×20 mL)
  8. dry with materialthe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a blue oil, which
  12. customwas purified by flash column chromatography (silica gel, eluting with 0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-388ceefed6064a029b57a87833463c09
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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