Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl ester → 5-[(5-fluoro-3-iodo-1H-indole-2-carbonyl)-amino]-pent-2-enoic acid ethyl ester

HRID 29786Notes

Reaction equation

HRID 29786 reaction equation
O=[CH:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([C:16]=1[I:17])=[CH:14][C:13]([F:18])=[CH:12][CH:11]=2)=[O:7].[C:19]([CH:24]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:21][CH2:22][CH3:23])=[O:20]>C1COCC1>[CH2:22]([O:21][C:19](=[O:20])[CH:24]=[CH:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[NH:9][C:10]2[C:15]([C:16]=1[I:17])=[CH:14][C:13]([F:18])=[CH:12][CH:11]=2)=[O:7])[CH3:23]

Participants

4

Reactant 2

HCID 70670Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl esterHCID 597892255-fluoro-3-iodo-1H-indole-2-carboxylic acid (3-oxo-propyl)-amide

Product 1

HCID 686370095-[(5-fluoro-3-iodo-1H-indole-2-carbonyl)-amino]-pent-2-enoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-fluoro-3-iodo-1H-indole-2-carboxylic acid (3-oxo-propyl)-amide, prepared as in reference 13, (5.86 g, 16.3 mmol) in THF (200 mL) is added (carbethoxymethylene) triphenylphosphorane (18 g, 51.7 mmol) at 0° C. The reaction is stirred at room temperature overnight. It is washed with saturated NH4Cl (200 mL) and extracted with Et2O (200 mL×2). The combined organic layers are washed with brine and dried. It is concentrated and purified by silica gel column chromatography and eluted with EtOAc-Hexanes to give 5-[(5-fluoro-3-iodo-1H-indole-2-carbonyl)-amino]-pent-2-enoic acid ethyl ester as the trans isomer; 1H NMR (DMSO-d6) δ 1.25 (t, 3H, J=6.8 Hz), 2.52 (t, 2H, J=6.8 Hz), 3.48 (q, 2H, J=5.6 Hz), 4.10 (q, 2H, 6.8 Hz), 5.96 (d, 1H, J=15.6 Hz), 6.96 (dt, 1H, J1=5.8 Hz, J2=15.6 Hz), 7.06-7.18 (m, 2H), 7.46 (dd, 1H, J1=4.0 Hz, J2=8.8 Hz), 8.11 (t, 1H, J=6.4 Hz), 12.10 (s, 1H); m/z [M++1] 431.0.

Workup

  1. washIt is washed with saturated NH4Cl (200 mL)
  2. extractionextracted with Et2O (200 mL×2)
  3. washThe combined organic layers are washed with brine
  4. customdried
  5. concentrationIt is concentrated
  6. custompurified by silica gel column chromatography
  7. washeluted with EtOAc-Hexanes

Sources & evidence

ORD record
ord-6456683d1f7340f8b79c091ecb484d04
Source dataset
uspto-grants-2008_09
Patent number
US07423031B2

Reaction notes

Loading…