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

HRID 2260483Notes

Reaction equation

HRID 2260483 reaction equation
[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]

Participants

6

Reactant 3

HCID 79724-Methylmorpholine2×HCID 11045256Boc-Val-Pro-OHHCID 131719225H-Val-CF2CF3.hydrochloride

Product 1

HCID 10075203Boc-Val-Pro-Val-CF2CF3Yield 88.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Procedure

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.

Workup

  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. additiondiluted with CH2Cl2 (100 ml)
  5. washThe organic phase was washed with 1 N HCl (3×75 ml)
  6. customDrying
  7. concentration(Na2SO4) and concentration
  8. customgave a colorless oil which

Sources & evidence

ORD record
ord-349954c467ad4eaeae96b6eb883473ad
Source dataset
uspto-grants-1995_12
Patent number
US05478811

Reaction notes

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