Water → HCID 86755689, compound

HRID 1872764Notes

Reaction equation

HRID 1872764 reaction equation
[CH2:1]([O:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[NH2:15])[CH3:2].[Cl:16][C:17]1[CH:18]=[C:19]([CH2:24][CH:25]2[CH2:30][C:29](=O)[CH2:28][CH2:27][N:26]2[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:20]=[CH:21][C:22]=1[Cl:23].[BH4-].[Na+].O>C(Cl)Cl.C(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[Cl:16][C:17]1[CH:18]=[C:19]([CH2:24][C@H:25]2[CH2:30][C@H:29]([NH:15][C:7]3[N:6]([CH2:5][CH2:4][O:3][CH2:1][CH3:2])[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[N:8]=3)[CH2:28][CH2:27][N:26]2[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:20]=[CH:21][C:22]=1[Cl:23].[Cl:16][C:17]1[CH:18]=[C:19]([CH2:24][C@H:25]2[CH2:30][C@@H:29]([NH:15][C:7]3[N:6]([CH2:5][CH2:4][O:3][CH2:1][CH3:2])[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[N:8]=3)[CH2:28][CH2:27][N:26]2[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:20]=[CH:21][C:22]=1[Cl:23]

Participants

9

Reactant 4

HCID 962WaterHCID 4311764Sodium borohydrideHCID 18687533HCID 18687533, compoundHCID 53948261HCID 53948261, compound

Product 2

HCID 86755689HCID 86755689, compoundHCID 86755690HCID 86755690, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

1-(2-ethoxyethyl)-1H-benzimidazol-2-amine (8.2 g) was added to (±)-ethyl 2-[(3,4-dichlorophenyl)methyl]-4-oxo-1-piperidinecarboxylate (13.2 g) in CH2Cl2 (20 ml). Titanium(IV)isopropoxide (13.64 g) was added and the mixture was stirred for 3 hours at RT. Sodiumborohydride (1.82 g) in ethanol (20 ml) was added and the reaction mixture was stirred overnight at RT. Water (20 ml) was added and the mixture was stirred for 5 minutes. CH2Cl2 (200 ml) was added and the mixture was stirred, dried, filtered, and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 98/2, upgrading to 97/3). The desired fractions were collected and the solvent was evaporated, yielding 2.6 g of (±)-ethyl trans-2-[(3,4-dichlorophenyl)methyl]-4-[[1-(2-ethoxyethyl)-1H-benzimidazol-2-yl]amino]-1-piperidinecarboxylate (interm. 25), and 6.2 g of (±)-ethyl cis-2-[(3,4-dichlorophenyl)methyl]-4-[[1-(2-ethoxyethyl)-1H-benzimidazol-2-yl]amino]-1-piperidinecarboxylate (interm. 26).

Workup

  1. stirringthe reaction mixture was stirred overnight at RT
  2. stirringthe mixture was stirred for 5 minutes
  3. stirringthe mixture was stirred
  4. customdried
  5. filtrationfiltered
  6. customthe filtrate was evaporated
  7. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 98/2, upgrading to 97/3)
  8. customThe desired fractions were collected
  9. customthe solvent was evaporated

Sources & evidence

ORD record
ord-f85eee9a45874e63a46dd7b4eb5eedc6
Source dataset
uspto-grants-2000_08
Patent number
US06110939

Reaction notes

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