4-Amino-2-fiuorobenzoylglutamic acid di-t-butyl ester → 4-(6,7-Bis(palmitoyloxy)-4-thiaheptanoyl)amino-2-fluorobenzoylglutamic acid di-t-butyl ester

HRID 1720826Notes

Reaction equation

HRID 1720826 reaction equation
[C:1]([O:5][C:6](=[O:28])[C@H:7]([CH2:19][CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][C:11]=1[F:17])([CH3:4])([CH3:3])[CH3:2].[C:29]([O:46][CH:47]([CH2:55][O:56][C:57](=[O:73])[CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH3:72])[CH2:48][S:49][CH2:50][CH2:51][C:52](O)=[O:53])(=[O:45])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44]>N1C=CC=CC=1.P(Cl)(Cl)Cl.O>[C:1]([O:5][C:6](=[O:28])[C@H:7]([CH2:19][CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:52](=[O:53])[CH2:51][CH2:50][S:49][CH2:48][CH:47]([O:46][C:29](=[O:45])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[CH2:55][O:56][C:57](=[O:73])[CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH3:72])=[CH:12][C:11]=1[F:17])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 2

HCID 100693194-Amino-2-fiuorobenzoylglutamic acid di-t-butyl esterHCID 105562786,7-Bis(palmitoyloxy)-4-thiaheptanoic acid

Product 1

HCID 537823564-(6,7-Bis(palmitoyloxy)-4-thiaheptanoyl)amino-2-fluorobenzoylglutamic acid di-t-butyl esterYield 87%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 24387Phosphorus trichlorideSolvent

Procedure

To a solution of 4-amino-2-fiuorobenzoylglutamic acid di-t-butyl ester (181 mg) in pyridine (2.3 ml), phosphorus trichloride (0.020 ml) was added, followed by stirring at room temperature for 2 hours. To this mixture, 6,7-bis(palmitoyloxy)-4-thiaheptanoic acid as obtained in Reference Example 24 (150 mg) was added, followed by stirring at room temperature for 24 hours. The reaction mixture was diluted with water, extracted with ethyl acetate. The extract was washed with a 5% aqueous solution of citric acid, a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, and dried over anhydrous sodium sulfate, and the solvent was distilled off. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to yield the title compound (205 mg, yield 87%) as a wax-like substance.

Workup

  1. additionwas added
  2. stirringby stirring at room temperature for 24 hours
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with a 5% aqueous solution of citric acid
  5. dry with materiala saturated aqueous solution of sodium hydrogen carbonate and saturated saline, and dried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off
  7. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-a602253f7cf64b2bb3e218a4f0aff160
Source dataset
uspto-grants-1996_04
Patent number
US05506267

Reaction notes

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