Phenylacetic Acid → Phenylacetylglutamine t-butyl ester

HRID 2372702노트

반응식

HRID 2372702 반응식
[C:1]1([CH2:7][C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N[C@H](C(O)=O)CCC(=O)N.ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.Cl.[C:45]([O:49][C:50](=[O:58])[C@H:51]([CH2:53][CH2:54][C:55](=[O:57])[NH2:56])[NH2:52])([CH3:48])([CH3:47])[CH3:46]>CN(C)C=O.C(N(CC)CC)C>[C:45]([O:49][C:50](=[O:58])[C@H:51]([CH2:53][CH2:54][C:55](=[O:57])[NH2:56])[NH:52][C:8](=[O:10])[CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([CH3:48])([CH3:46])[CH3:47]

참가 물질

8

반응물 5

HCID 999Phenylacetic Acid2회HCID 5961L-GlutamineHCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 15602445H-Gln-OtBu hydrochloride

생성물 1

HCID 53814505Phenylacetylglutamine t-butyl ester

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매

실험 절차

As shown in reaction scheme I (FIG. 1), phenylacetic acid 1 (1250 mg; 1.84 mmol) was coupled to a protected glutamine 4 (protected in this case by a lower alkyl such as t-butyl group) by first dissolving the phenyl acetic acid in anhydrous dimethylformamide (8 ml). N-hydroxysuccinimide 2 (254 mg; 2.2 mmol) was added followed by addition of dicyclohexylcarbodiimide (456 mg; 2.2 mmol) to produce N-succinimidphenylacetate 3. The reaction mixture was stirred for ten hours and precipitated dicyclohexyl urea was filtered off. The filtrate containing 3 was returned to a reaction flask to which a carboxy-protected glutamine such as L-glutamine t-butyl-ester hydrochloride 4 (439 mg; 1.84 mmol) was added. pH was adjusted to 9 with triethylamine, and the reaction mixture was stirred for 24 hours to produce phenylacetylglutamine t-butyl ester 5. Precipitated crystals were filtered off, and the filtrate containing 5 after concentration in vacuum was purified by column chromatography on silica gel using ethyl acetate-methanol (95:5) as an eluent. Yield 299 mg of desired material, mp. 132°-133° C. 1H-NMR (60 MHz) (CDCl3) δ ppm: 1.4 (s,9H); 1.8-2.4 (mult,4H); 3.6 (s,2H); 4.5 (mult,1H); 5.5 (broad,1H); 6.3 (mult,2H); 7.3 (s,5H). Mass Spectrum (DEI/DIP): 321 (M+H)+, 320 M+, 264 (M-C4H8)+, 247 (M-OC4H9)+. The t-butyl ester 5 (295 mg; 0.924 mmole) of phenylacetylglutamine was deprotected (i.e., the t-butyl carboxy protecting group was removed) by dissolving 5 in methylene chloride (4 ml) and adding trifluoroacetic acid (4 ml). After 45 minutes, the reaction mixture was evaporated in vacuum and the oily residue crystallized from tetrahydrofurane (THF), to give colorless crystals of phenylacetyl glutamine 6. 1H-NMR(300 MHz)(CDCl3 /CD3OD) δ ppm 1.9-2.05 (mult,1H); 2.13-2.36 (mult,3H); 3.58 (s,2H); 4.5 (mult,1H); 7.23-7.38 (mult,5H); Mass Spectrum (pos.FAB, MeOH):265 (M+H)+ (100%).

후처리

  1. customto produce N-succinimidphenylacetate 3
  2. customprecipitated dicyclohexyl urea
  3. filtrationwas filtered off
  4. additionThe filtrate containing 3
  5. customwas returned to a reaction flask to which
  6. stirringthe reaction mixture was stirred for 24 hours

출처 및 근거

ORD 기록
ord-b8fccd9b39a54eb69ab2a523d74f6539
출처 데이터셋
uspto-grants-1992_03
특허 번호
US05100807

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