4-Methylmorpholine → HCID 131719740, compound

HRID 1955584Notes

Reaction equation

HRID 1955584 reaction equation
C(C[N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15]C=2C(C2C=CC=CC=2)=N[CH:7]([NH:22]C(OCC2C=CC=CC=2)=O)[C:6]1=[O:33])(O)=O.C[N:35]1CCOCC1.C(OC(Cl)=O)C(C)C.CO[C:51](=O)[C@H:52]([C@H:54](CC)[CH3:55])N>O1CCCC1>[NH2:22][C@H:7]([C:6]([N:5]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=[N:35]1)=[O:33])[C@H:52]([CH2:54][CH3:55])[CH3:51]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 75735L-Isoleucine, methyl esterHCID 11113037HCID 11113037, compound

Product 1

HCID 131719740HCID 131719740, compoundYield 274.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the benzodiazepin-2-one 29 (0.55 g, 1.23 mmol), in tetrahydrofuran (4 mL) at -20° C. under argon, was added NMM (0.14 mL, 1.23 mmol) followed by isobutylchloroformate (9.16 mL, 1.23 mmol). The mixture was stirred for 5 minutes, and then 0.14 mL (1.23 mmol) of NMM was added, followed by isoleucine methyl ester (0.22 g, 1.23 mmol) in tetrahydrafuran. This solution was stirred for 1 hour at -20° C., then 2 hours at room temperature. Tetrahydrafuran was removed in vacuum and the resulting solid was dissolved in ethylacetate, and the salts filtered off. The ethyl acetate extract was washed with 5% citric acid, 5% sodium bicarbonate solution, water, brine and dried over MgSO4. Solvent evaporated to give 0.70 g of the crude 2-isoleucyl diazepine 30. This was chromatographed on silica gel column using 40% ethyl acetate/60% hexane to give 0.59 g of pure 30 (92% yield).

Workup

  1. stirringThis solution was stirred for 1 hour at -20° C.
  2. custom2 hours
  3. customat room temperature
  4. customTetrahydrafuran was removed in vacuum
  5. dissolutionthe resulting solid was dissolved in ethylacetate
  6. filtrationthe salts filtered off
  7. extractionThe ethyl acetate extract
  8. washwas washed with 5% citric acid, 5% sodium bicarbonate solution, water, brine
  9. dry with materialdried over MgSO4
  10. customSolvent evaporated

Sources & evidence

ORD record
ord-08d5e09e26724de3994f5130a257fcf0
Source dataset
uspto-grants-1998_07
Patent number
US05776902

Reaction notes

Loading…