4-Methylmorpholine → 2-[(N-benzyloxycarbonyl-trans-4-hydroxy-L-prolyl)-L-valyl]amino-6-methylbenzoic acid

HRID 1590817Notes

Reaction equation

HRID 1590817 reaction equation
ClC(OCC(C)C)=O.[CH2:9]([O:16][C:17]([N:19]1[CH2:26][C@H:25]([OH:27])[CH2:24][C@H:20]1[C:21]([OH:23])=O)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN1CCOCC1.[CH3:35][C:36]1[C:41]([C:42]([OH:44])=[O:43])=[C:40]([NH:45][C:46](=[O:52])[C@H:47]([CH:49]([CH3:51])[CH3:50])[NH2:48])[CH:39]=[CH:38][CH:37]=1.C(OC(N1CCC[C@H]1C(N[C@@H](C(NC1C=CC=C(C)C=1C(O)=O)=O)C(C)C)=O)=O)C1C=CC=CC=1>CN(C)C=O.O1CCCC1>[CH2:9]([O:16][C:17]([N:19]1[CH2:26][C@H:25]([OH:27])[CH2:24][C@H:20]1[C:21]([NH:48][C@H:47]([C:46]([NH:45][C:40]1[CH:39]=[CH:38][CH:37]=[C:36]([CH3:35])[C:41]=1[C:42]([OH:44])=[O:43])=[O:52])[CH:49]([CH3:51])[CH3:50])=[O:23])=[O:18])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

8

Reactant 5

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 3915171-(Phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylateHCID 537310472-(N-benzyloxycarbonyl-L-prolyl-D-valyl)amino-6-methylbenzoic acidHCID 541805686-methyl-2-(L-valylamino)benzoic acid

Product 1

HCID 186513032-[(N-benzyloxycarbonyl-trans-4-hydroxy-L-prolyl)-L-valyl]amino-6-methylbenzoic acidYield 98.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Isobutyl chloroformate (0.23 ml) was added to a tetrahydrofuran solution (3.5 ml) containing N-benzyloxycarbonyl-trans-4-hydroxy-L-proline (463 mg) and N-methylmorpholine (0.19 ml) at -15° C., and the mixture was stirred for 0.5 hour. An N,N-dimethylformamide solution (2.5 ml) containing 6-methyl-2-(L-valylamino)benzoic acid (291 mg) and N-methylmorpholine (0.15 ml) was added dropwise to the above mixture at -15° C., and the resultant mixture was stirred at -15° C. for 0.5 hour and then at room temperature for two hours. The reaction mixture was treated by the same procedures as in item (c) of Example 1 to obtain 2-[(N-benzyloxycarbonyl-trans-4-hydroxy-L-prolyl)-L-valyl]amino-6-methylbenzoic acid (570 mg).

Workup

  1. additionwas added dropwise to the above mixture at -15° C.
  2. waitat room temperature for two hours

Sources & evidence

ORD record
ord-3ae1d452f4754967b9bd9abde39b4efa
Source dataset
uspto-grants-1993_04
Patent number
US05204462

Reaction notes

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