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Thioglycolic Acid → (S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-((S)-1-phenyl-propylamino)-propionic acid methyl ester

HRID 391781
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HRID 391781 반응식
[CH3:1][O:2][C:3](=[O:54])[C@@H:4]([N:32](S(C1C=CC([N+]([O-])=O)=CC=1)(=O)=O)[C@H:33]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH2:34][CH3:35])[CH2:5][C:6]1[CH:31]=[CH:30][C:9]2[O:10][C@@H:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=4)=[CH:16][CH:15]=3)[CH2:12][O:13][C:8]=2[CH:7]=1.SCC(O)=O.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[CH3:1][O:2][C:3](=[O:54])[C@@H:4]([NH:32][C@H:33]([C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)[CH2:34][CH3:35])[CH2:5][C:6]1[CH:31]=[CH:30][C:9]2[O:10][C@@H:11]([C:14]3[CH:15]=[CH:16][C:17]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=4)=[CH:18][CH:19]=3)[CH2:12][O:13][C:8]=2[CH:7]=1
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참가 물질

5

반응물 3

HCID 1133Thioglycolic AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 66719419(S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-[(4-nitro-benzenesulfonyl)-((S)-1-phenyl-propyl)-amino]-propionic acid methyl ester

생성물 1

HCID 58327321(S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-((S)-1-phenyl-propylamino)-propionic acid methyl ester
수율 64.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

(S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-[(4-nitro-benzenesulfonyl)-((S)-1-phenyl-propyl)-amino]-propionic acid methyl ester (1.8 g) was dissolved in 30 mL dry DMF, then 505 μL (670 mg) mercaptoacetic acid and 2.6 mL (2.6 g) DBU were added at rt. The reaction stirred for 3 h, then was partitioned between saturated aqueous NaHCO3 and diethyl ether. The organic layer was washed successively with aqueous NaHCO3, water, and brine, then was dried with Na2SO4 and evaporated. The residue was purified by silica gel flash chromatography (9:1 to 8:2 hexanes/EtOAc) to give 893 mg desired product after drying. 1H NMR (400 MHz, acetone-d6): 7.71 (d, 1H), 7.61 (d, 1H), 7.50-7.42 (m, 3H), 7.27-7.15 (m, 5H), 7.09 (m, 2H), 6.80 (d, 1H), 6.67 (d, 1H), 6.61 (m, 1H), 5.19 (s, 2H), 5.10 (m, 1H), 4.34 (m, 1H), 4.02 (m, 1H), 3.63 (s, 3H), 3.47 (t, 1H), 3.15 (t, 1H), 2.75 (m, 2H), 2.10 (s, 1H), 1.69-1.48 (m, 2H), 0.78 (t, 3H).

후처리

  1. customwas partitioned between saturated aqueous NaHCO3 and diethyl ether
  2. washThe organic layer was washed successively with aqueous NaHCO3, water, and brine
  3. dry with materialwas dried with Na2SO4
  4. customevaporated
  5. customThe residue was purified by silica gel flash chromatography (9:1 to 8:2 hexanes/EtOAc)

출처 및 근거

ORD 기록
ord-1f93701acfbb4b06b7eea6c7ae2e5b0b
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08383644B2

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