Tetrahydrofuran → N-[(1,1-Dimethylethoxy)carbonyl]-L-alanyl-L-proline phenylmethyl ester

HRID 435401Notes

Reaction equation

HRID 435401 reaction equation
C1COCC1.[NH:6]1[CH2:20][CH2:19][CH2:18][C@H:7]1[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9].Cl.C1C=CC2N(O)N=NC=2C=1.[NH:32]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C@H:33]([C:35](O)=[O:36])[CH3:34]>CN(C=O)C>[NH:32]([C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])[C@H:33]([C:35]([N:6]1[CH2:20][CH2:19][CH2:18][C@H:7]1[C:8]([O:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:9])=[O:36])[CH3:34]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 757711-HydroxybenzotriazoleHCID 85082Tert-butoxycarbonylalanineHCID 2733413Proline benzyl ester hydrochloride

Product 1

HCID 13068139N-[(1,1-Dimethylethoxy)carbonyl]-L-alanyl-L-proline phenylmethyl esterYield 100.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

THF (200 ml), H-Pro-OBzl.HCl (48.3 g, 0.2 M) and HOBT (27.0 g, 0.2 M) were added to BOC-Ala-OH (37.8 g, 0.2 M); DMF (100 ml) was added, and WSCI (36.6 ml, 0.2 M) was added dropwise at 0° C. After stirring at 0° C. for one hour and at room temperature overnight, the solvent was distilled off in vacuo. The residue was dissolved in ethyl acetate (500 ml), washed three times with 5% sodium bicarbonate solution, three times with 1 N HCl and three times with water, in that order, dried with anhydrous magnesium sulfate and concentrated in vacuo. The residue was dissolved in a small amount of benzene and charged on a column of silica gel (250 g) packed with benzene. Elution was carried out with benzene (1 l.), benzene-ethyl acetate (10:1) (1 l.) and benzene-ethyl acetate (1:1) (1 l.), and the corresponding fractions were collected and checked by TLC and concentrated in vacuo to obtain the oily substance [24] (75.55 g, yield: 100%).

Workup

  1. additionWSCI (36.6 ml, 0.2 M) was added dropwise at 0° C
  2. distillationthe solvent was distilled off in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (500 ml)
  4. washwashed three times with 5% sodium bicarbonate solution, three times with 1 N HCl and three times with water
  5. dry with materialin that order, dried with anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in a small amount of benzene
  8. additioncharged on a column of silica gel (250 g)
  9. washElution
  10. customthe corresponding fractions were collected
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2a9c19d83c5447d383cd7a378a67b87b
Source dataset
uspto-grants-1983_08
Patent number
US04400316

Reaction notes

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