Triethylamine → 6-(3-Adamantan-1-yl-ureido)-hexanoic acid benzyl ester

HRID 563973노트

반응식

HRID 563973 반응식
[C:1]1([CH3:11])[CH:6]=CC(S(O)(=O)=O)=C[CH:2]=1.[CH2:12]([O:19][C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.ClC(Cl)([O:31]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.Cl.Cl.C[N:50]([CH3:59])[C:51]1[CH:58]=[CH:57][C:54](CN)=[CH:53][CH:52]=1>ClCCl>[CH2:12]([O:19][C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:59]([NH:50][C:51]12[CH2:52][CH:53]3[CH2:54][CH:57]([CH2:11][CH:1]([CH2:6]3)[CH2:2]1)[CH2:58]2)=[O:31])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 27346334-(aminomethyl)-N,N-dimethylaniline dihydrochlorideHCID 13077333Hexanoic acid, 6-amino-, phenylmethyl ester, 4-methylbenzenesulfonate (1:1)

생성물 1

HCID 670063306-(3-Adamantan-1-yl-ureido)-hexanoic acid benzyl ester수율 180.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a vigorously stirred suspension of 6-amino-hexanoic acid benzyl ester toluene-4-sulfonic acid (0.786 g, 2.00 mmol) and triphosgene (0.200 g, 0.667 mmol) in dichloromethane (30 mL) at −78° C. under inert atmosphere, was added triethylamine (1.0 mL, 7.188 mmol, in 10 mL dichloromethane) dropwise via additional funnel over a period of 2 hours. The cooling bath was removed and the resulting reaction was allowed to stir at room temperature for 1 hour, after which time, 4-Dimethylaminobenzylamine dihydrochloride (0.303 g, 2.00 mmol) was added to the reaction mixture. After stirring overnight, the mixture was washed with brine (20 mL) and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over sodium sulfate and the solvent was evaporated. The residue was purified using flash column chromatography (silica gel 60, CH2Cl2/EtOAc=6:1 to 4:1) to afford 6-(3-Adamantan-1-yl-ureido)-hexanoic acid benzyl ester 0.481 g (61% yield). 1H NMR (300 MHz, CDCl3) δ (ppm) 7.34 (m, 5H), 5.11 (s, 2H), 4.61 (t, J=5.7 Hz, 1H), 4.43 (s, 1H), 3.08 (dt, J=6.9, 5.7 Hz, 2H), 2.35 (t, J=7.5 Hz, 2H), 2.04 (m, 3H), 1.94 (m, 6H), 1.65 (m, 8H) 1.46 (m, 2H) 1.31 (m, 2H). 13C NMR (75 MHz, CDCl3) 6 (Ppm) 173.5, 157.4, 135.9, 128.5, 128.2, 128.1, 66.1, 50.6, 42.5, 39.8, 36.4, 34.1, 29.9, 29.5, 26.4, 24.5.

후처리

  1. customThe cooling bath was removed
  2. customthe resulting reaction
  3. stirringAfter stirring overnight
  4. washthe mixture was washed with brine (20 mL)
  5. extractionthe aqueous layer was extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. customthe solvent was evaporated
  8. customThe residue was purified

출처 및 근거

ORD 기록
ord-a174f4b993e3424084f164e8141efc9e
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08067600B2

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