Sodium hydride → HCID 53735669, compound

HRID 330438Notes

Reaction equation

HRID 330438 reaction equation
C[CH:2]1[CH:7](C)[CH2:6][CH2:5][CH:4]([NH:9][C:10](=[O:45])[C@H:11]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[CH:33][CH:32]=2)[NH:12][C:13](=[O:29])[C:14]2[CH:19]=[CH:18][C:17]([CH2:20][NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:16][CH:15]=2)[CH2:3]1.[H-].[Na+].N1C=CC(CCl)=CC=1>CN(C)C=O>[CH:4]1([NH:9][C:10](=[O:45])[C@H:11]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)=[CH:33][CH:32]=2)[NH:12][C:13](=[O:29])[C:14]2[CH:15]=[CH:16][C:17]([CH2:20][NH:21][C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])=[CH:18][CH:19]=2)[CH2:5][CH2:6][CH2:7][CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 745714-(Chloromethyl)pyridineHCID 54354000N-[4-(t-butyloxycarbonyl)aminomethylbenzoyl]-4-benzyloxy-L-phenylalanine 3,4-dimethylcyclohexylamide

Product 1

HCID 53735669HCID 53735669, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of the above compound (II) (1.70 g), palladium black (0.20 g), cyclohexene (6 ml), and ethanol (50 ml) was reacted under reflux of ethanol. After cooling, the solid was filtered off and the filtrate was concentrated to obtain N-(t-butyloxycarbonyl)-4-hydroxy-L-phenylalanine 4-pipecolylamide (III) (1.36 g). The compound (III) was dissolved, without purification, in N,N-dimethylformamide (20 ml). To this solution was added oily sodium hydride (60% content) (0.16 g), followed by stirring at room temperature for 30 minutes. To this solution was added a solution of 4-picolyl chloride (0.50 g) in N,N-dimethylformamide (5 ml) and the reaction was carried out at room temperature for 7 hours. Ice water was added to the reaction mixture and the resultant oily proudct was extracted with ethyl acetate. After a conventional post-treatment, N-(t-butyloxycarbonyl)-4-(4-picolyloxy)-L-phenylalanine 4-pipecolylamide (IV) (1.20 g) was obtained. From the compound (IV), N-(trans-4-aminomethylcyclohexylcarbonyl)-4-(4-picolyloxy)-L-phenylalanine-4-pipecolylamide (0.85 g) following the procedure of Example 6.

Workup

  1. waitthe reaction was carried out at room temperature for 7 hours
  2. extractionthe resultant oily proudct was extracted with ethyl acetate

Sources & evidence

ORD record
ord-728e9c92fc304127a600243bf1863c65
Source dataset
uspto-grants-1990_01
Patent number
US04895842

Reaction notes

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