Hydrochloric Acid → Sampatrilat

HRID 567938Notes

Reaction equation

HRID 567938 reaction equation
C(OC([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C@@H:16]([C:22]([NH:24][CH2:25][C@@H:26]([C:56]([O:58]C(C)(C)C)=[O:57])[CH2:27][C:28]1([C:33]([NH:35][C@H:36]([C:49]([O:51]C(C)(C)C)=[O:50])[CH2:37][C:38]2[CH:43]=[CH:42][C:41]([O:44]C(C)(C)C)=[CH:40][CH:39]=2)=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29]1)=[O:23])[NH:17][S:18]([CH3:21])(=[O:20])=[O:19])=O)C1C=CC=CC=1.Cl>C(OCC)(=O)C.O>[C:56]([C@H:26]([CH2:25][NH:24][C:22](=[O:23])[C@H:16]([CH2:15][CH2:14][CH2:13][CH2:12][NH2:11])[NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[CH2:27][C:28]1([C:33]([NH:35][C@H:36]([C:49]([OH:51])=[O:50])[CH2:37][C:38]2[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=2)=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29]1)([OH:58])=[O:57]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86756335HCID 86756335, compound

Product 1

HCID 6324648SampatrilatYield 22.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a cooled (10° C.) solution of tert-butyl (S,S,S)-N-(1-[3-(N6-benzyloxycarbonyl-N2-mesyllysylamino)-2-(tert-butoxycarbonyl)propyl]-1-cyclopentylcarbonyl)-O4-tert-butyltyrosinate (13.3 g, 15.0 mmol) in ethyl acetate (27 ml) was added a 5.1M solution of hydrogen chloride in ethyl acetate (70 ml) (357 mmol of HCl). After 30 minutes the initially clear solution deposited a tar. The mixture was stirred at room temperature for 18 hours. The clear solution was decanted off from the tar and the tar triturated with ethyl acetate (75 ml) to give a sticky solid. The decantation and trituration were repeated 5 times to give a hygroscopic solid which was dissolved in water (12 ml). The resulting aqueous solution was washed twice with ethyl acetate, basified with aqueous sodium hydroxide solution to pH 4.0, seeded with the compound of Example 1 and stirred at 45-50° C. for 42 hours. The off-white solids were collected by filtration, washed with water and acetone and dried to give the title compound (1.95 g), m.p. 237-238° C.

Workup

  1. customThe clear solution was decanted off from the tar
  2. customthe tar triturated with ethyl acetate (75 ml)
  3. customto give a sticky solid
  4. customto give a hygroscopic solid which
  5. washThe resulting aqueous solution was washed twice with ethyl acetate
  6. stirringstirred at 45-50° C. for 42 hours
  7. filtrationThe off-white solids were collected by filtration
  8. washwashed with water and acetone
  9. customdried

Sources & evidence

ORD record
ord-92b68e3f250d47f693dda2b910285bd4
Source dataset
uspto-grants-2001_01
Patent number
US06180665B2

Reaction notes

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