Citric Acid → HCID 22942068, compound

HRID 850870Notes

Reaction equation

HRID 850870 reaction equation
[F:1][C:2]([F:49])([F:48])[CH2:3][CH:4]([N:10]([CH2:27][C:28]1[C:43]([O:44][CH3:45])=[CH:42][C:31]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])=[CH:30][C:29]=1[O:46][CH3:47])[C:11](=[O:26])[C@H:12]([CH2:22][CH:23]([CH3:25])[CH3:24])[NH:13][C:14](=[O:21])[C@H:15]([C:17]([CH3:20])([CH3:19])[CH3:18])[NH2:16])[CH:5]([O:8][CH3:9])[O:6][CH3:7].[C:50](=O)([O-])[O-:51].[K+].[K+].[CH:56]1[C:68]2[CH:67]([CH2:69][O:70]C(ON3C(=O)CCC3=O)=O)[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[C:60]=2[CH:59]=[CH:58][CH:57]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO.O>[CH:65]1[C:66]2[CH:67]([CH2:69][O:70][C:50]([NH:16][C@H:15]([C:14]([NH:13][C@H:12]([C:11]([N:10]([CH2:27][C:28]3[C:43]([O:44][CH3:45])=[CH:42][C:31]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[CH:30][C:29]=3[O:46][CH3:47])[CH:4]([CH:5]([O:8][CH3:9])[O:6][CH3:7])[CH2:3][C:2]([F:48])([F:1])[F:49])=[O:26])[CH2:22][CH:23]([CH3:24])[CH3:25])=[O:21])[C:17]([CH3:20])([CH3:18])[CH3:19])=[O:51])[C:68]3[C:60](=[CH:59][CH:58]=[CH:57][CH:56]=3)[C:61]=2[CH:62]=[CH:63][CH:64]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 22942076HCID 22942076, compound

Product 1

HCID 22942068HCID 22942068, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

4.0 g (5.7 mmol) of ethyl 5-[4-[[N-[3,3,3-trifluoro-1(RS)-(dimethoxymethyl)propyl]-N-[N-(3-methyl-L-valyl)-L-leucyl]-amino]methyl]-3,5-dimethoxyphenoxy]-valerate were dissolved in 40 ml of methanol. 2.4 g (17.3 mmol) of potassium carbonate and 8.0 ml of water were then added and the mixture was stirred for 2 days at room temperature. The solvent was removed by evaporation and the residue was dissolved in 20 ml of water and 20 ml of dioxan. 2.9 g (8.6 mmol) of N-[(9-fluorenyl)-methoxycarbonyloxy]-succinimide were then added and the mixture was stirred for 3 hours. The mixture was adjusted to pH 3 with 10% citric acid and then washed with three equal aliquots of dichloromethane. The combined organic layers were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and the filtrate was evaporated. The residue was chromatographed on silica gel using 4% tert-butyl methyl ether in dichloromethane for the elution. There were obtained 5.12 g of 5-[4-[[N-[N-[N-[(9-fluorenyl)methoxycarbonyl]-3-methyl-L-valyl]-L-leucyl]-N-[3,3,3-trifluoro-1(RS)-(dimethoxymethyl)propyl]amino]methyl]-3,5-dimethoxyphenoxy]valeric acid as a white foam; MS: m/e 870.8 [M+H-MeOH], 888.7 [M+H-CH3 ], 889.7 [M-CH3 ]902.7 [M+H], 924.7 [M+Na].

Workup

  1. customThe solvent was removed by evaporation
  2. dissolutionthe residue was dissolved in 20 ml of water
  3. stirringthe mixture was stirred for 3 hours
  4. washwashed with three equal aliquots of dichloromethane
  5. washThe combined organic layers were washed with saturated sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. customthe filtrate was evaporated
  9. customThe residue was chromatographed on silica gel using 4% tert-butyl methyl ether in dichloromethane for the elution

Sources & evidence

ORD record
ord-3feeb36287e5451194e2d80e6b4ae472
Source dataset
uspto-grants-2000_01
Patent number
US06018020

Reaction notes

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