Hydrochloric Acid → HCID 13306583, compound

HRID 2412324Notes

Reaction equation

HRID 2412324 reaction equation
[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([N:9]1[CH2:16][CH2:15][CH2:14][C@H:10]1[C:11]([OH:13])=O)=[O:8].[CH3:17]N1[CH2:23][CH2:22][O:21]CC1.[CH2:24]([O:26]C(Cl)=O)[CH3:25].Cl.[NH2:31][C@H:32]([C:43]([NH:45][C@H:46]([C:50]([O:52][CH3:53])=[O:51])[CH:47]([CH3:49])[CH3:48])=[O:44])[CH2:33][C:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[NH:36][CH:35]=1>O1CCCC1.CN(C)C=O>[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([N:9]1[CH2:16][CH2:15][CH2:14][C@H:10]1[C:11]([NH:31][C@H:32]([C:43]([NH:45][C@H:46]([C:50]([O:52][CH3:53])=[O:51])[CH:47]([CH3:49])[CH3:48])=[O:44])[CH2:33][C:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[NH:36][CH:35]=1)=[O:13])=[O:8].[CH:22]([OH:21])([CH3:23])[CH3:24].[CH:24]([O:26][CH:15]([CH3:14])[CH3:16])([CH3:17])[CH3:25]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 10928Ethyl chloroformateHCID 7020177HCID 7020177, compoundHCID 133065895-Oxo-L-prolyl-L-proline

Product 2

HCID 13306583HCID 13306583, compoundHCID 21202047Isopropyl alcohol isopropyl ether

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5.66 g (25 mmol) of Pyr-Pro-OH (III) in 60 ml of anhydrous tetrahydrofuran, 2.81 ml (25 mmol) N-methyl-morpholine and 2.48 ml (25 mmol) of ethylchloroformate were successively added at -12° C. After stirring for 2 minutes, a cold solution of 8.85 g (25 mmol) of HCl.H-Trp-Val-OMe (XI) and 2.81 ml (25 mmol) of N-methylmorpholine in 60 ml of dimethylformamide was added. The reaction mixture was stirred for 1 h at -12° C. and for 2 h at 0°-15° C., then filtered to remove salts and evaporated in vacuo. The crude product was purified by column chromatography on silica gel (Merck) 0.040-0.063 mm with an eluent of methylene dichloride:methanol:water in a ratio of 92:8:1 by volume. A 8.37 g (63.7% yield) amount of XII was obtained from isopropyl alcohol/diisopropyl ether. m.p. 120° C. [α]D24 =-76.3° (c=1 MeOH); RfB 0.21; RfC 0.56; Amino acid ratio:Glu 1.00; Pro 0.98; Val 1.00.

Workup

  1. stirringThe reaction mixture was stirred for 1 h at -12° C. and for 2 h at 0°-15° C.
  2. filtrationfiltered
  3. customto remove salts
  4. customevaporated in vacuo
  5. customThe crude product was purified by column chromatography on silica gel (Merck) 0.040-0.063 mm with an eluent of methylene dichloride

Sources & evidence

ORD record
ord-6cd5996598074a908e3f2a5a1e082673
Source dataset
uspto-grants-1985_01
Patent number
US04491541

Reaction notes

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