Trifluoroacetic acid → (S)-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione

HRID 2191223Notes

Reaction equation

HRID 2191223 reaction equation
[O:1]([CH2:8][C@@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1C(OC(C)(C)C)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[O:28]=[C:29]1[C:37](=[O:38])[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([S:39](Cl)(=[O:41])=[O:40])[CH:35]=2)[NH:30]1>C(Cl)Cl.C1COCC1>[O:1]([CH2:8][C@@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[S:39]([C:34]1[CH:35]=[C:36]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29](=[O:28])[C:37]2=[O:38])(=[O:40])=[O:41])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 10636271(S)-tert-Butyl 2-(phenoxymethyl)pyrrolidine-1-carboxylateHCID 159089472,3-Dioxoindoline-5-sulfonyl chloride

Product 1

HCID 9821545(S)-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dioneYield 84.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 9 (1.46 g, 5.2 mmol) in CH2Cl2 (5 mL) was added trifluoroacetic acid (5 mL) at 0° C. The mixture was stirred at 0° C. for 15 min. After evaporation of the solvent in vacuo, CH2Cl2 (15 mL) and triethylamine (2 mL) were added, then a solution of 6 (1.44 g, 5.9 mmol) in THF (25 mL) was added at 0° C. The reaction mixture was stirred overnight at room temperature. The solvent was evaporated in vacuo, then ethyl acetate (150 mL) was added, washed with water (50 mL×2) and saturated NaCl (50 mL), and dried over Na2SO4. After evaporation of the ethyl acetate, the crude product was purified with ether to afford 1.7 g (84%) of 10 as a yellow solid, mp 204.5-205.9° C. 1H NMR (300 MHz, CDCl3) δ 8.94 (s, 1H), 7.77 (dd, J=8.25 Hz, J=2.1 Hz, 1H), 7.67 (s, 1H), 7.02 (t, J=8.7 Hz, 2H), 6.84 (d, J=8.1 Hz, 1H), 6.69 (t, J=7.2 Hz, 1H), 6.63 (d, J=7.8 Hz, 2H), 3.89 (m, 1H), 3.75-3.66 (m, 2H), 3.23 (m, 1H), 2.96 (m, 1H), 1.72 (m, 2H), 1.54-1.42 (m, 2H). LRMS (FAB) m/e: 387.1 (M+H, 100). Anal. Calcd for C19.N2O5S: C, 59.06, H, 4.70; N, 7.25. Found: C, 58.99, H, 4.74, N, 7.11.

Workup

  1. customAfter evaporation of the solvent in vacuo, CH2Cl2 (15 mL) and triethylamine (2 mL)
  2. additionwere added
  3. stirringThe reaction mixture was stirred overnight at room temperature
  4. customThe solvent was evaporated in vacuo
  5. additionethyl acetate (150 mL) was added
  6. washwashed with water (50 mL×2) and saturated NaCl (50 mL)
  7. dry with materialdried over Na2SO4
  8. customAfter evaporation of the ethyl acetate
  9. customthe crude product was purified with ether

Sources & evidence

ORD record
ord-d227becdb8df4ce79f0b3a00bea9d21e
Source dataset
uspto-grants-2012_12
Patent number
US08329686B2

Reaction notes

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