Succinic anhydride → Succinic acid mono-(4-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-1-{6-[17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxycarbonylamino]-hexanoyl}-pyrrolidin-3-yl) ester

HRID 2403017Notes

Reaction equation

HRID 2403017 reaction equation
[CH3:1][CH:2]([CH:9]1[C:25]2([CH3:26])[CH:12]([CH:13]3[CH:22]([CH2:23][CH2:24]2)[C:21]2([CH3:27])[C:16]([CH2:17][CH:18]([O:28][C:29](=[O:69])[NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][C:36]([N:38]4[CH2:42][CH:41]([OH:43])[CH:40]([CH:44]([C:63]5[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=5)[O:45][CH:46]([C:55]5[CH:60]=[CH:59][C:58]([O:61][CH3:62])=[CH:57][CH:56]=5)[C:47]5[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=5)[CH2:39]4)=[O:37])[CH2:19][CH2:20]2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH2:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7].[C:70]1(=[O:76])[O:75][C:73](=[O:74])[CH2:72][CH2:71]1.C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl>[CH3:54][O:53][C:50]1[CH:51]=[CH:52][C:47]([CH:46]([C:55]2[CH:56]=[CH:57][C:58]([O:61][CH3:62])=[CH:59][CH:60]=2)[O:45][CH:44]([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH:40]2[CH2:39][N:38]([C:36](=[O:37])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][NH:30][C:29]([O:28][CH:18]3[CH2:17][C:16]4[C:21]([CH3:27])([CH:22]5[CH:13]([CH2:14][CH:15]=4)[CH:12]4[C:25]([CH3:26])([CH:9]([CH:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH:6]([CH3:7])[CH3:8])[CH2:10][CH2:11]4)[CH2:24][CH2:23]5)[CH2:20][CH2:19]3)=[O:69])[CH2:42][CH:41]2[O:43][C:70](=[O:76])[CH2:71][CH2:72][C:73]([OH:75])=[O:74])=[CH:48][CH:49]=1

Participants

6

Reactant 3

HCID 7922Succinic anhydrideHCID 8471TriethylamineHCID 131728221(6-{3-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-pyrrolidin-1-yl}-6-oxo-hexyl)-carbamic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl Ester

Product 1

HCID 131728222Succinic acid mono-(4-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-1-{6-[17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxycarbonylamino]-hexanoyl}-pyrrolidin-3-yl) esterYield 91.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Referring to scheme 17, Compound 66(12 g, 12.69 mmol) was mixed with succinic anhydride (1.9 g, 19 mmol) and DMAP (1.56 g, 13 mmol) and dried in a vacuum at 40° C. overnight. The mixture was dissolved in anhydrous dichloromethane (50 mL), triethylamine (2 g, 3.6 mL, 26 mmol) was added and the solution was stirred at room temperature under argon atmosphere for 16 h. It was then diluted with dichloromethane (100 mL) and washed with ice cold aqueous citric acid (5% wt., 100 mL) and water (2×100 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated to dryness. The crude product was purified by column chromatography to afford compound 68 as white solid (12.1 g, 91% yield; Rf=0.5 in 10% MeOH/CHCl3).

Workup

  1. customdried in a vacuum at 40° C. overnight
  2. dissolutionThe mixture was dissolved in anhydrous dichloromethane (50 mL)
  3. washwashed with ice cold aqueous citric acid (5% wt., 100 mL) and water (2×100 mL)
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. concentrationconcentrated to dryness
  6. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-394ab2a0882344b08d78cc6cafe310c6
Source dataset
uspto-grants-2014_08
Patent number
US08796436B2

Reaction notes

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