Sodium Hydroxide → L-Proline, N-(3-methoxy-1,2,4-thiadiazol-5-yl)-L-leucyl-

HRID 1275605Notes

Reaction equation

HRID 1275605 reaction equation
C[O:2][C:3](=[O:24])[C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9](=[O:23])[C@H:10]([CH2:19][CH:20]([CH3:22])[CH3:21])[NH:11][C:12]1[S:16][N:15]=[C:14]([O:17][CH3:18])[N:13]=1.[OH-].[Na+]>CO>[CH3:18][O:17][C:14]1[N:13]=[C:12]([NH:11][C@H:10]([C:9]([N:5]2[CH2:6][CH2:7][CH2:8][C@H:4]2[C:3]([OH:24])=[O:2])=[O:23])[CH2:19][CH:20]([CH3:22])[CH3:21])[S:16][N:15]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 12052376N-(3-methoxy-1,2,4-thiadiazol-5-yl)-l-leucyl-l-proline methyl ester

Product 1

HCID 9862877L-Proline, N-(3-methoxy-1,2,4-thiadiazol-5-yl)-L-leucyl-Yield 89%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To an ice-cooled solution of N-(3-methoxy-[1,2,4]thiadiazol-5-yl)-L-leucyl-L-proline methyl ester (0.68 g, 1.91 mmol) in methanol (10 mL) was added a solution of 1N sodium hydroxide (2.4 mL, 2.4 mmol). The resulting mixture was stirred in ice for 3 h, then at room temperature for 16 h. Volatile materials were removed in vacuo and the residue was dissolved in water (10 mL) and washed with ethyl acetate. The aqueous layer was collected and acidified with 1N HCl solution (pH ca. 5.6) as a voluminous white precipitate separated. The mixture was extracted into ethyl acetate (6×25 mL), and the combined organic layers was dried (sodium sulfate), filtered and concentrated to a light yellow foam. Trituration with diethyl ether gave N-(3-methoxy-[1,2,4]thiadiazol-5-yl)-L-leucyl-L-proline as a white solid (0.58 g, 89%). M.p. foamed at 78° C. and melted at 89.0-92.0C.; 1H-NMR (CDCl3) δ7.65 (br. s, 1H, NHCH), 4.70 (br. t, 1H, NHCH), 4.49 (t, J=5.3 Hz, 1H, CHCO2), 3.97 (s, 3H, OMe), 3.56-3.58 (m, 2H), 2.03-2.21 (m, 3H), 1.60-1.76 (m, 3H), 0.76-0.99 (m, 1H), 0.99 (d, J=6.5 Hz, 3H, Me), 0.96 (d, J=6.2 Hz, 3H, Me); MS (m/z) 343 (M+ +1), 228, 200, 102, 83.

Workup

  1. waitat room temperature for 16 h
  2. customVolatile materials were removed in vacuo
  3. dissolutionthe residue was dissolved in water (10 mL)
  4. washwashed with ethyl acetate
  5. customThe aqueous layer was collected
  6. customseparated
  7. extractionThe mixture was extracted into ethyl acetate (6×25 mL)
  8. dry with materialthe combined organic layers was dried (sodium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated to a light yellow foam

Sources & evidence

ORD record
ord-a3b057b418e04c70881bcd5737be405c
Source dataset
uspto-grants-2000_12
Patent number
US06162791

Reaction notes

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