Hydrochloric Acid → (2S,4R)-1-(2-{[(benzyloxy)carbonyl]amino}acetyl)-4-hydroxypyrrolidine-2-carboxylic acid

HRID 250796

반응식

HRID 250796 반응식
[OH:1][C@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.C(=O)([O-])O.[Na+].[CH2:15]([O:22][C:23]([NH:25][CH2:26][C:27](C1CC(=O)N(O)C1=O)=[O:28])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl>O.C(COC)OC.C(OCC)(=O)C>[CH2:15]([O:22][C:23]([NH:25][CH2:26][C:27]([N:5]1[CH2:6][C@H:2]([OH:1])[CH2:3][C@H:4]1[C:7]([OH:9])=[O:8])=[O:28])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 5810L-HydroxyprolineHCID 516892Sodium BicarbonateHCID 22037183N-benzyloxycarbonyl-glycyl-N-hydroxysuccinimide

생성물 1

HCID 58088404(2S,4R)-1-(2-{[(benzyloxy)carbonyl]amino}acetyl)-4-hydroxypyrrolidine-2-carboxylic acid수율 70%

시약·촉매·용매 3

HCID 962Water용매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

실험 절차

trans-4-Hydroxy-L-proline 1 (0.28 g, 2.13 mmol) and sodium hydrogen carbonate (0.18 g, 2.13 mmol) were dissolved in water (3 cm3) at room temperature. N-benzyloxycarbonyl-glycyl-N-hydroxysuccinimide 2 (0.44 g, 1.44 mmol) in dimethoxyethane (3 cm3) was added dropwise over a period of 5 min. The solution was stirred for 2.5 then acidified with conc. hydrochloric acid (38%) to pH 1. The solution was placed in a refrigerator overnight. Ethyl acetate (2×20 cmr3) was added and the resulting organic layers dried (MgSO4), filtered and evaporated under reduced pressure to yield a light pinky foam, which was purified by flash column chromatography (10% methanol/methylene chloride) to produce acid 3 (0.32 g, 70%) as a clear foam. Acid 3 was shown to be an 77:23 trans:cis mixture of conformers by 1H NMR analysis (the ratio was estimated from the integration of the signals at (δ 4.33-4.38 and 4.52-4.54, assigned to the Proα-H of the major and minor conformers respectively): [α]D −75.5 (c 0.08 in MeOH); OH (300 MHz; CD3OD) 1.89-1.94 (0.77H, m, Proβ-HAHB), 2.08-2.14 (1H, m, Proβ-HAHB), 2.14-2.16* (0.23H, m, Proβ-HAHB), 3.17-3.20 (1H, m, Proδ-HAHB), 3.53-3.57 (1H, m, Proδ-HAHB), 3.73-3.78 (1H, d, J 17.1, Glyα-HAHB), 3.87-3.93 (1H, d, J 17.1, Glyα-HAHB), 4.20-4.30* (0.23H, m, Proγ-H), 4.33-4.38 (1.54H, m, Proγ-H and Proα-H), 4.52-4.54* (0.23H, t, J 7.0, Proα-H) 4.94 (2H, s, OCH2Ph) and 7.11-7.23 (5H, m, Ph); δC (75 MHz, CD3OD) 39.0 (CH2, Proβ-C), 41.3* (CH2, Pro-C), 44.2* (CH2, Proδ-C), 44.8 (CH2, Proδ-C), 55.9 (CH2, Glyα-C), 56.2* (CH2, Glyα-C), 59.5* (CH, Proα-C), 60.1 (CH, Proα-C), 68.5 (CH2, OCH2Ph), 68.7* (CH2, OCH2Ph), 69.7* (CH, Proγ-C), 71.7 (CH, Proγ-C), 129.6 (CH, Ph), 129.7 (CH, Ph), 130.2 (CH, Ph), 138.9 (quat., Ph), 159.6 (quat., NCO2), 170.1 (quat., Gly-CO), 171.6* (quat., Gly-CO), 175.9* (quat., CO2H) and 176.3 (quat., CO2H),; m/z (FAB+) 323.1240 (M+.C16H20N2O5 requires 320.1243).

후처리

  1. customwas placed in a refrigerator overnight
  2. dry with materialthe resulting organic layers dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated under reduced pressure
  5. customto yield a light pinky foam, which
  6. customwas purified by flash column chromatography (10% methanol/methylene chloride)

출처 및 근거

ORD 기록
ord-f5d038e2f31f410a9697f2a96c6ef311
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863304B2

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