Ethyl Acetate → 2-({4-[(2-Chloro-4-nitrophenyl)diazenyl]phenyl}ethylamino)ethyl (5S,3R)-5-{[bis(4-methoxyphenyl)phenylmethoxy]methyl}-3-hydroxypyrrolidinecarboxylate

HRID 47960Notes

Reaction equation

HRID 47960 reaction equation
[OH:1][C@@H:2]1[CH2:6][C@@H:5]([CH2:7][OH:8])[N:4]([C:9]([O:11][CH2:12][CH2:13][NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([N:23]=[N:24][C:25]3[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][C:26]=3[Cl:34])=[CH:19][CH:18]=2)=[O:10])[CH2:3]1.CO[C:37]1[C:38](OC)=[C:39]([CH:54]=[CH:55][CH:56]=1)[C:40](Cl)([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.[C:59](=[O:62])(O)[O-].[Na+].[C:64](OCC)(=[O:66])C>N1C=CC=CC=1>[CH3:64][O:66][C:56]1[CH:55]=[CH:54][C:39]([C:40]([C:41]2[CH:46]=[CH:45][C:44]([O:62][CH3:59])=[CH:43][CH:42]=2)([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[O:8][CH2:7][C@H:5]2[N:4]([C:9]([O:11][CH2:12][CH2:13][NH:14][CH2:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]([N:23]=[N:24][C:25]4[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][C:26]=4[Cl:34])=[CH:21][CH:22]=3)=[O:10])[CH2:3][C@H:2]([OH:1])[CH2:6]2)=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 66624882Dimethoxytrityl chlorideHCID 865847182-({4-[(2-Chloro-4-nitrophenyl)diazenyl]phenyl}ethylamino)ethyl(5S,3R)-3-hydroxy-5-(hydroxymethyl)pyrrolidinecarboxylate

Product 1

HCID 865847172-({4-[(2-Chloro-4-nitrophenyl)diazenyl]phenyl}ethylamino)ethyl (5S,3R)-5-{[bis(4-methoxyphenyl)phenylmethoxy]methyl}-3-hydroxypyrrolidinecarboxylate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 3 (9.1 g, 18.53 mmol) in 130 ml of anhydrous pyridine was added 6.26 g of dimethoxytrityl chloride. The solution was stirred for 3 h. at room temperature and then poured into 300 ml of 5% sodium bicarbonate solution. The mixture was extracted with ethyl acetate (2×300 ml) and the combined extracts were dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography eluting with a gradient of 20-0% hexane in ethyl acetate followed by a gradient of 0-2% methanol in ethyl acetate. The chromatography eluent also contained 1% triethylamine. The pure product fractions were combined affording an amorphous solid: 12.66 g (86%); TLC (ethyl acetate), Rf=0.44. 1H NMR (DMSO-d6) δ8.45 (1H, s), 8.26 (1H, d, J=8.9 Hz), 7.82 (3H, m), 7.27 (4H, m), 7.16 (5H, m), 6.95-6.79 (6H, m), 4.95 (1H, m), 4.32 (1H, m), 4.14 (1H, m), 3.99 (2H, m), 3.73 (1H, m), 3.69 (6H, s), 3.56 (1H, m), 3.40-3.30 (2H, m), 3.14 (1H, m), 2.10-1.82 (2H, m), 1.16 (3H, m), 1.06 (3H, t, J=6.5 Hz). Anal. Calcd for C43H44ClN5O8*0.2 H2O: C, 64.73; H, 5.61; N, 8.78. Found: C, 65.08; H, 5.70; N, 8.31.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (2×300 ml)
  2. dry with materialthe combined extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with a gradient of 20-0% hexane in ethyl acetate
  7. customThe pure product fractions were combined affording an amorphous solid

Sources & evidence

ORD record
ord-a0e8b649e6504271983fb5ef60f4557c
Source dataset
uspto-grants-2004_03
Patent number
US06699975B2

Reaction notes

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