tert-butyl N-(2-hydroxyethyl)carbamate → {4-[4-(2-tert-Butoxycarbonylaminoethoxy)phenyl]butyl}carbamic acid benzyl ester

HRID 81320

반응식

HRID 81320 반응식
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH2:15]([O:22][C:23](=[O:36])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[C:37]([O:41][C:42](=[O:47])[NH:43][CH2:44][CH2:45]O)([CH3:40])([CH3:39])[CH3:38]>C1COCC1>[CH2:15]([O:22][C:23](=[O:36])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:45][CH2:44][NH:43][C:42]([O:41][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:47])=[CH:31][CH:30]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

참가 물질

5

반응물 3

HCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 5363146Diisopropyl azodicarboxylateHCID 11637991N-Cbz4-(4-hydroxyphenyl)butylamine

생성물 1

HCID 67364654{4-[4-(2-tert-Butoxycarbonylaminoethoxy)phenyl]butyl}carbamic acid benzyl ester수율 73.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
25 °C

실험 절차

Diisopropylazodicarboxylate (132 mL) was added dropwise over 45 minutes to a stirring mixture of [4-(4-hydroxyphenyl)butyl]carbamic acid benzyl ester (50 g, 0.167 mol), (2-hydroxyethyl)carbamic acid tert-butyl ester (103.4 mL, 0.668 mol), and THF (150 mL) with ice-methanol bath cooling from 15 to 35° C. When the exothermic reaction ceased, the cooling bath was removed, and the reaction was allowed to stir at room temperature overnight. The solvent was evaporated at reduced pressure, and the residue was applied to a 1 kg column of silica gel and eluted with methylene chloride. The chromatography was repeated twice. The residue after evaporation was washed with hexanes (1.5 L), and the resulting solid was re-crystallized from a mixture of hexanes and methylene chloride (4:1, 1 L) to afford 54 g (73%) of the pure product as a white solid. A second crop yielded an additional 10 g (13%) of the product. 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9H), 1.56 (m, 4H), 2.56 (t, 2H), 3.20 (m, 2H), 3.50 (m, 2H), 3.98 (t, 2H), 4.75 (br s, 1H), 5.00 (br s, 1H), 5.09 (s, 2H), 6.80 (d, 2H), 7.06 (d, 2H), 7.34 (m, 5H).

후처리

  1. customWhen the exothermic reaction
  2. customthe cooling bath was removed
  3. customThe solvent was evaporated at reduced pressure
  4. washeluted with methylene chloride
  5. customThe residue after evaporation
  6. washwas washed with hexanes (1.5 L)
  7. customthe resulting solid was re-crystallized from a mixture of hexanes and methylene chloride (4:1, 1 L)

출처 및 근거

ORD 기록
ord-1b7a4abb290c4e25b96720121e1343f8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846688B2

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