1,1'-(Chlorophenylmethylene)bis(4-methoxybenzene) → (9H-fluoren-9-yl)methyl 2-((bis(4-methoxyphenyl)(phenyl)-methoxy)methyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 888745Notes

Reaction equation

HRID 888745 reaction equation
[OH:1][CH:2]1[CH2:6][N:5]([C:7]([O:9][CH2:10][CH:11]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)=[O:8])[CH:4]([CH2:24][OH:25])[CH2:3]1.[CH3:26][O:27][C:28]1[CH:49]=[CH:48][C:31]([C:32](Cl)([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)=[CH:30][CH:29]=1>N1C=CC=CC=1>[CH3:40][O:39][C:36]1[CH:35]=[CH:34][C:33]([C:32]([C:31]2[CH:30]=[CH:29][C:28]([O:27][CH3:26])=[CH:49][CH:48]=2)([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:25][CH2:24][CH:4]2[CH2:3][CH:2]([OH:1])[CH2:6][N:5]2[C:7]([O:9][CH2:10][CH:11]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)=[O:8])=[CH:38][CH:37]=1

Participants

4

Reactant 2

HCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)HCID 22629839(9H-fluoren-9-yl)methyl 4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 69094046(9H-fluoren-9-yl)methyl 2-((bis(4-methoxyphenyl)(phenyl)-methoxy)methyl)-4-hydroxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

(9H-Fluoren-9-yl)methyl 4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate (10.6 g, 31.2 mmoles) is coevaporated twice with anhydrous pyridine (50 mL each) and then dissolved in anhydrous pyridine (200 mL). The stirred solution is chilled in an ice bath, and 4,4′-dimethoxytritylchloride (11.0 g, 32.5 mmoles) is added in three approximately equal portions at thirty minute intervals. When the addition is complete, the flask is stoppered and place at 4° C. for 16 hours. The mixture is then evaporated to a thick yellow syrup, which is dissolved in toluene (100 mL), filtered and evaporated. The residue is dissolved in methylene chloride (350 mL) and washed successively with cold aqueous citric acid (10% [w/v], 150 mL), saturated aqueous sodium bicarbonate (150 mL) and saturated aqueous sodium chloride (150 mL). The methylene chloride solution is dried over anhydrous sodium sulfate, filtered and evaporated to a yellow foam. The crude product is purified on silica gel (500 mL bed volume) eluting with ethyl acetate:hexanes:triethylamine (50:50:1 [v/v/v], 1300 mL; then 67:33:1 [v/v/v], 1800 mL), then ethyl acetate:triethylamine (99:1 [v/v], 1000 mL). Fractions containing pure product by thin layer chromatography are pooled and evaporated to an off-white amorphous solid which is dried well in vacuo. The yield is 17.7 g (88%).

Workup

  1. temperatureThe stirred solution is chilled in an ice bath
  2. additionWhen the addition
  3. customThe mixture is then evaporated to a thick yellow syrup, which
  4. dissolutionis dissolved in toluene (100 mL)
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue is dissolved in methylene chloride (350 mL)
  8. washwashed successively with cold aqueous citric acid (10% [w/v], 150 mL), saturated aqueous sodium bicarbonate (150 mL) and saturated aqueous sodium chloride (150 mL)
  9. dry with materialThe methylene chloride solution is dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customevaporated to a yellow foam
  12. customThe crude product is purified on silica gel (500 mL bed volume)
  13. washeluting with ethyl acetate:hexanes:triethylamine (50:50:1 [v/v/v], 1300 mL
  14. additionFractions containing pure product by thin layer chromatography
  15. customevaporated to an off-white amorphous solid which
  16. customis dried well in vacuo

Sources & evidence

ORD record
ord-863141dc3b57426b84787c0d1934c08e
Source dataset
uspto-grants-2012_08
Patent number
US08252755B2

Reaction notes

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