Methanol → 7-(2-{1-[1-(3-Benzyloxy-phenyl)-2-ethoxycarbonyl-ethyl]-1H-indol-5-yloxy}-ethyl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester

HRID 24006Notes

Reaction equation

HRID 24006 reaction equation
[I-].[Sm+2].[I-].[C:4]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH2:21][CH2:22][O:23][C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[N:29]([C:33]([C:40]3[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH2:47][C:48]5[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=5)[CH:41]=3)=[CH:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH:28]=[CH:27]4)[N:19]=2)[CH2:14][CH2:13][CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5].CN(C)P(N(C)C)(N(C)C)=O.CO.[Cl-].[NH4+]>C(O)C>[C:4]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH2:21][CH2:22][O:23][C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[N:29]([CH:33]([C:40]3[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH2:47][C:48]5[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=5)[CH:41]=3)[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH:28]=[CH:27]4)[N:19]=2)[CH2:14][CH2:13][CH2:12]1)=[O:10])([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 5

HCID 887MethanolHCID 12679HexamethylphosphoramideHCID 25517Ammonium ChlorideHCID 668211417-(2-{1-[1-(3-benzyloxy-phenyl)-2-ethoxycarbonyl-vinyl]-1H-indol-5-yloxy}-ethyl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl esterHCID 178506586HCID 178506586, compound

Product 1

HCID 668214097-(2-{1-[1-(3-Benzyloxy-phenyl)-2-ethoxycarbonyl-ethyl]-1H-indol-5-yloxy}-ethyl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl esterYield 493.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Samarium(II) iodide [0.1 M in THF] (14.8 mL, 14.8 mmol) was added to a solution of 7-(2-{1-[1-(3-benzyloxy-phenyl)-2-ethoxycarbonyl-vinyl]-1H-indol-5-yloxy}-ethyl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (0.10 g, 0.15 mmol), hexamethylphosphoramide (0.39 mL, 2.22 mmol) and either ethanol or methanol (10 equivalents) and stirred at room temperature overnight. Saturated ammonium chloride (20 mL) was added to the reaction and the crude product was extracted with ethyl acetate (3×20 mL). The crude mixture was then purified via column chromatography in silica gel (20% ethyl acetate in hexane) to give the title compound (0.50 g, 50% yield). 1H NMR (CDCl3) δ 7.28-7.22 (m, 5H), 7.13 (m, 4H), 7.08 (d, 1H, J=3.2 Hz), 6.86 (m, 1H), 6.79-6.69 (m, 4H), 6.35 (d, 1H, J=3.2 Hz), 5.99 (t, 1H, J=7.5 Hz), 4.98 (s, 2H), 4.29 (t, 2H, J=6.9 Hz), 3.96 (q, 2H, J=7.1 Hz), 3.68 (m, 2H), 3.18-3.10 (m, 4H), 2.66 (m, 2H), 1.85 (m, 2H), 1.45 (s, 9H), 1.01 (t, 3H, J=7.1 Hz).

Workup

  1. extractionthe crude product was extracted with ethyl acetate (3×20 mL)
  2. customThe crude mixture was then purified via column chromatography in silica gel (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-d05016fac233425dad76ccec7fcdfbad
Source dataset
uspto-grants-2005_02
Patent number
US06855722B2

Reaction notes

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