Water → {2-[2-(2-{2-[2-(4-{2-[2-(2-{2-[2-(9H-fluoren-9-yl-methoxycarbonylamino)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-phenoxy)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}acetic acid tert-butyl ester

HRID 2075639Notes

Reaction equation

HRID 2075639 reaction equation
[C:1]([O:5][C:6](=[O:46])[CH2:7][O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][NH2:45])=[CH:26][CH:25]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])ON1C(=O)CC([CH2:55][CH:56]2[C:68]3[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=3[C:62]3[C:57]2=[CH:58][CH:59]=[CH:60]C=3)C1=O.C(N(CC)CC)C.[OH2:79].C1[CH2:84][O:83][CH2:82]C1>>[C:1]([O:5][C:6](=[O:46])[CH2:7][O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][C:24]1[CH:25]=[CH:26][C:27]([O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][N:45]([CH:55]2[C:60]3[CH:59]=[CH:58][CH:57]=[CH:62][C:63]=3[C:64]3[C:56]2=[CH:68][CH:67]=[CH:66][CH:65]=3)[C:82]([O:83][CH3:84])=[O:79])=[CH:28][CH:29]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 5

HCID 962WaterHCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 67089348[2-(2-{2-[2-(2-{4-[2-(2-{2-[2-(2-Amino-ethoxy)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-phenoxy}-ethoxy)-ethoxy]-ethoxy}-ethoxy)-ethoxy]acetic acid tert-butyl esterHCID 71304114(9H-fluoren-9-yl)methyl-2,5-dioxopyrrolidin-1-yl carbonate

Product 1

HCID 67089303{2-[2-(2-{2-[2-(4-{2-[2-(2-{2-[2-(9H-fluoren-9-yl-methoxycarbonylamino)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-phenoxy)-ethoxy]-ethoxy}-ethoxy)-ethoxy]-ethoxy}acetic acid tert-butyl esterYield 84%

Procedure

A solution of the crude product of Compound 28 obtained in Production Example 40 (175 mg, 0.311 mmol) in THF (1.2 ml) was cooled with ice, a solution of 9-fluorenylmethylsuccinimidyl carbonate (115 mg, 0.34 mmol) in THF (0.5 ml) was added thereto, triethylamine (62 mg, 0.62 mmol, 85 μl) was further added, and this was followed by stirring for 45 minutes. Water was added thereto to stop the reaction, after which extraction from ethyl acetate was conducted, and the combined organic phases were washed with saturated brine and dried with sodium sulfate. Filtration and concentration under reduced pressure were conducted, after which the concentrate was purified by silica gel column chromatography (Yamazen YFLC Gel, eluent; ethyl acetate-ethyl acetate solution containing 10% methanol) to yield Compound 29 (colorless oil 196 mg, 84%).

Workup

  1. temperaturewas cooled with ice
  2. customthe reaction
  3. extractionafter which extraction from ethyl acetate
  4. washthe combined organic phases were washed with saturated brine
  5. dry with materialdried with sodium sulfate
  6. filtrationFiltration and concentration under reduced pressure
  7. customafter which the concentrate was purified by silica gel column chromatography (Yamazen YFLC Gel, eluent; ethyl acetate-ethyl acetate solution containing 10% methanol)

Sources & evidence

ORD record
ord-627b71967a98460d88b4730b5243a184
Source dataset
uspto-grants-2011_04
Patent number
US07919653B2

Reaction notes

Loading…