4-Methylmorpholine → HCID 44360270, compound

HRID 613236Notes

Reaction equation

HRID 613236 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][C:9]([OH:11])=O)[CH:2]=1.CN1CCOCC1.C(N(CC)CC)C.C(OC(Cl)=O)C(C)C.[NH2:34][C@H:35]([C:39]([N:41]1[CH2:61][CH2:60][CH2:59][C@H:42]1[C:43]([NH:45][C@H:46]([C:50]([C:52]([C:55]([F:58])([F:57])[F:56])([F:54])[F:53])=[O:51])[CH:47]([CH3:49])[CH3:48])=[O:44])=[O:40])[CH:36]([CH3:38])[CH3:37].Cl>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][C:9]([NH:34][C@H:35]([C:39]([N:41]2[CH2:61][CH2:60][CH2:59][C@H:42]2[C:43]([NH:45][CH:46]([CH:47]([CH3:48])[CH3:49])[C:50](=[O:51])[C:52]([F:53])([F:54])[C:55]([F:56])([F:57])[F:58])=[O:44])=[O:40])[CH:36]([CH3:37])[CH3:38])=[O:11])[CH:2]=1

Participants

7

Reactant 5

HCID 79724-Methylmorpholine2×HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 2596243-(Pyridin-3-yl)propanoic acidHCID 73347173HCID 73347173, compound

Product 1

HCID 44360270HCID 44360270, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Suspend 3-(3-pyridyl)propionic acid (174 mg, 1.15 mmol, Walker, F. A. et al., J. Amer. Chem. Soc., 102, 5530-5538 (1980)) in methylene chloride (15 mL). Add N-methylmorpholine (0.38 mL, 3.45 mmol) and triethylamine (0.32 mL, 2.30 mmol), and cool the resulting clear, colorless solution to -18° C. Add isobutylchloroformate (0.15 mL, 1.15 mmol) and stir for 20 minutes. Subsequently add N-methylmorpholine (0.13 mL, 1.15 mmol) and H-Val-Pro-Val-CF2CF3.hydrochloride (520 mg, 1.15 mmol) and stir at -20° C. for 1 hour. Allow reaction mixture to warm to room temperature, dilute the reaction mixture with additional methylene chloride (35 mL) and successively wash with 1N HCl (3×20 mL), saturated NaHCO3 (2×20 mL), and brine (1×20 mL). Dry and concentrate the crude product. Purify the crude product by flash chromatography (75:25::acetone:EtOAc) to give the title compound as a white solid foam. (Yield: 470 mg, 74%, 3:1::LLL:LLD).

Workup

  1. customAllow reaction mixture
  2. washsuccessively wash with 1N HCl (3×20 mL), saturated NaHCO3 (2×20 mL), and brine (1×20 mL)
  3. customDry
  4. concentrationconcentrate the crude product
  5. customPurify the crude product by flash chromatography (75:25::acetone:EtOAc)

Sources & evidence

ORD record
ord-1f6a5d71653e4270866ea9c49c97bc54
Source dataset
uspto-grants-1999_12
Patent number
US06008196

Reaction notes

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