4-Methylmorpholine → Boc-Val-Pro-Val-CF2CF3

HRID 1385879노트

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HRID 1385879 반응식
[NH:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:2]([C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)=[O:7])[CH:3]([CH3:5])[CH3:4].CN1CCOCC1.[NH2:30][C@H:31]([C:35]([C:37]([C:40]([F:43])([F:42])[F:41])([F:39])[F:38])=[O:36])[CH:32]([CH3:34])[CH3:33].Cl>C(Cl)Cl.CC#N>[NH:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:2]([C:6]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([NH:30][C@H:31]([C:35]([C:37]([C:40]([F:41])([F:42])[F:43])([F:38])[F:39])=[O:36])[CH:32]([CH3:33])[CH3:34])=[O:12])=[O:7])[CH:3]([CH3:4])[CH3:5]

참가 물질

6

반응물 3

HCID 79724-Methylmorpholine2회HCID 11045256Boc-Val-Pro-OHHCID 131719225H-Val-CF2CF3.hydrochloride

생성물 1

HCID 10075203Boc-Val-Pro-Val-CF2CF3수율 88.1%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매2회

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온도
-16 °C

실험 절차

To a stirred solution of Boc—Val—Pro—OH (1.10 g, 3.5 mmole) in CH2Cl2 (20 ml) under argon, cooled to −17° C., was added NMM (0.40 ml, 3.68 mmole). After 5 minutes, 1 equivalent (0.45 ml, 3.5 mmole) of IBCF was added and a light suspension formed several minutes later. After 20 minutes NMM (0.4 ml, 3.68 mmol) was added followed by a suspension of H-Val-CF2CF3.HCl (0.88 g, 3.50 mol) in CH2Cl2 (10 ml) plus CH3CN (10 ml) dropwise (from an addition funnel) over ca. 15 minutes. The reaction was stirred at −14 to −18° C. for 1 hour and then the cooling bath was removed. The reaction was allowed to warm to room temperature (ca. 40 min.) and diluted with CH2Cl2 (100 ml). The organic phase was washed with 1 N HCl (3×75 ml), satd. NaHCO3 (2×75 ml), and brine (50 ml). Drying (Na2SO4) and concentration gave a colorless oil which was placed under high vacuum to give the desired product as a white foam (1.59 g, 88%). Elemental analysis; calculated for C22H34F5N3O5: %C=51.26; %H=6.65; %N=8.15. Found: %C=50.80; %H=6.57; %N=7.85.

후처리

  1. addition1 equivalent (0.45 ml, 3.5 mmole) of IBCF was added
  2. customa light suspension formed several minutes later
  3. customthe cooling bath was removed
  4. temperatureto warm to room temperature (ca. 40 min.)
  5. additiondiluted with CH2Cl2 (100 ml)
  6. washThe organic phase was washed with 1 N HCl (3×75 ml)
  7. customDrying
  8. concentration(Na2SO4) and concentration
  9. customgave a colorless oil which

출처 및 근거

ORD 기록
ord-d1ff70e34bf34e878d931a039c9f84f7
출처 데이터셋
uspto-grants-2001_07
특허 번호
US06265381B1

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