Hydrochloric Acid → 2-[[(4-Methylphenyl)sulfonyl]amino]-6-[[(phenylmethoxy)carbonyl]amino]hexanoic acid

HRID 1728777

반응식

HRID 1728777 반응식
[C:1]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C@@H:16]([C:18]([OH:20])=[O:19])[NH2:17])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1.Cl>[OH-].[Na+].O1CCOCC1.C(OCC)(=O)C>[CH3:31][C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH:17][CH:16]([CH2:15][CH2:14][CH2:13][CH2:12][NH:11][C:1]([O:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:2])[C:18]([OH:20])=[O:19])(=[O:29])=[O:28])=[CH:23][CH:22]=1

참가 물질

7

반응물 3

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 1715626epsilon-(Benzyloxycarbonyl)-L-lysine

생성물 1

HCID 140824522-[[(4-Methylphenyl)sulfonyl]amino]-6-[[(phenylmethoxy)carbonyl]amino]hexanoic acid수율 81,024.5%

시약·촉매·용매 3

HCID 8857Ethyl Acetate용매HCID 14798Sodium Hydroxide용매2회HCID 312751,4-Dioxane용매

반응 조건

온도
0 °C

실험 절차

Nε-Carbobenzyloxy-L-lysine (30.0g, 0.107 mmol) was dissolved in a solution of 2N NaOH (60 mL) and dioxane (150 mL) under nitrogen. After about 15 minutes at room temperature, the mixture was cooled to about 0° C. and subsequently treated with additional 2N NaOH (60 mL) and p-toluenesulfonyl chloride (20.4g, 0.107 mmol) in 5g portions over about 15 minutes. The mixture was stirred at about 0° C. for about 1 hour and at room temperature for about 18 hours before it was neutralized to pH 6 with 1N HCl. The mixture was then diluted with ethyl acetate and the organic phase was separated and washed with brine. The aqueous phase was extracted twice more with ethyl acetate and the combined organic phases were treated further as mentioned above. Following drying and solvent evaporation of the combined organic phases, the residue was first pre-columned on silica gel (elution with 10% methanol in dichloromethane) and subsequently recrystallized from ethyl acetate/hexanes (2:1 ) to give 37.67g (81%) of the title compound as a white solid, m.p. 120°-121° C.; 1H NMR (CDCl3) δ 8.37 (v br s, 0.5H), 7.71 (d, J=8.0 Hz, 2H), 7.32 (s, 5H), 7.23 (d, J=7.6 Hz, 2H), 6.49 and 4.89 (2m, 1H), 5.73 (d, J=8.4 Hz, 1H) , 5.10 and 5.04 (2s, 2H) , 3.91 (m, 1H) , 3.17-3.02 (m, 2H), 2.35 (s, 3H), 1.73-1.66 (m, 2H), 1.40-1.24 (m, 4H); 13C NMR (CDCl3) ppm 199.88, 175.06, 174.57, 158.37, 156.89, 143.66, 136.86, 136.32, 129.66, 128.54, 128.10, 127.19, 67.47, 66.89, 55.28, 40.95, 40.44, 32.25, 29.10, 28.75, 21.77, 21.46; IR (KBr, cm-1) 3382, 3264, 2950, 1738, 1656, 1550, 1334, 1286, 1160, 1092, 818, 678, 568; MS m/z (MH+) 435.1590, obsd 435.1595.

후처리

  1. customthe organic phase was separated
  2. washwashed with brine
  3. extractionThe aqueous phase was extracted twice more with ethyl acetate
  4. additionthe combined organic phases were treated further
  5. customFollowing drying
  6. customsolvent evaporation of the combined organic phases
  7. customsubsequently recrystallized from ethyl acetate/hexanes (2:1 )

출처 및 근거

ORD 기록
ord-04fa57e0be9e43539db4442f7eb2eda0
출처 데이터셋
uspto-grants-1994_07
특허 번호
US05328932

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