Phthalic Anhydride → (2S)3-Benzyloxycarbonylamino-2-phthalimidopropionic acid

HRID 1643376노트

반응식

HRID 1643376 반응식
C1(NC2CCCCC2)CCCCC1.[CH2:14]([O:21][C:22]([NH:24][CH2:25][C@H:26]([NH:30][C:31]([O:33]C(C)(C)C)=O)[C:27]([OH:29])=[O:28])=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C1(=O)O[C:41](=[O:42])[C:40]2=[CH:44][CH:45]=[CH:46][CH:47]=[C:39]12>ClCCl.Cl.C1(C)C=CC=CC=1>[CH2:14]([O:21][C:22]([NH:24][CH2:25][C@H:26]([N:30]1[C:31](=[O:33])[C:39]2=[CH:47][CH:46]=[CH:45][CH:44]=[C:40]2[C:41]1=[O:42])[C:27]([OH:29])=[O:28])=[O:23])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

참가 물질

6

반응물 2

HCID 6811Phthalic AnhydrideHCID 2755949Boc-Dap(Z)-OH.DCHA

생성물 1

HCID 18396554(2S)3-Benzyloxycarbonylamino-2-phthalimidopropionic acid

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매HCID 1140Toluene용매HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

A solution of (2S)3-benzyloxycarbonylamino-2-tert-butoxycarbonylaminopropionic acid dicyclohexylamine salt (3 g, 5.8 mmol) in dichloromethane (200 ml) was washed four times with 1M HCl solution, dried (MgSO4) and concentrated. The resulting oil was dissolved in dry dichloromethane (35 ml), cooled to 0° C. and treated with trifluoroacetic acid (35 ml). This solution was stirred at 0° C. for 1.5 h then evaporated to dryness. Dichloromethane (50 ml) was added to the residue then removed under vacuum. This process repeated six times to afford a white solid. The white solid was suspended in toluene (50 ml), treated with powdered phthalic anhydride (940 mg, 6.35 mmol) and refluxed for 18 h. The resulting solution was concentrated to afford an oil which was purified by flash chromatography (2-10% methanol/dichloromethane) to afford 266, 2.01 g (94%) as a white powder: IR (KBr) 3600-2500br, 1776, 1714, 1530, 1469, 1455, 1392, 1263, 1131, 722; 1H NMR (CDCl3) δ 7.83 (2H, m), 7.72 (2H, m), 7.29 (5H, m), 5.41 (1H, m), 5.03 (2H, s), 3.90 (2H, m); MS (ES−), 367 (M−1).

후처리

  1. dry with materialdried (MgSO4)
  2. concentrationconcentrated
  3. dissolutionThe resulting oil was dissolved in dry dichloromethane (35 ml)
  4. additiontreated with trifluoroacetic acid (35 ml)
  5. customthen evaporated to dryness
  6. additionDichloromethane (50 ml) was added to the residue
  7. customthen removed under vacuum
  8. customto afford a white solid
  9. temperaturerefluxed for 18 h
  10. concentrationThe resulting solution was concentrated
  11. customto afford an oil which
  12. customwas purified by flash chromatography (2-10% methanol/dichloromethane)

출처 및 근거

ORD 기록
ord-d8a4c96bb4e84996974e5ca7963bcd8a
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08119631B2

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