Ammonia → cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-(4-oxopentyl)4-piperidinyl]-2,2-dimethyl-7-benzofurancarboxamide hemihydrate

HRID 1598591Notes

Reaction equation

HRID 1598591 reaction equation
[NH2:1][C:2]1[C:7]2[CH2:8][C:9]([CH3:12])([CH3:11])[O:10][C:6]=2[C:5]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][C:25]3([CH3:30])OCC[O:26]3)[CH2:18][C@H:17]2[O:31][CH3:32])=[O:14])=[CH:4][C:3]=1[Cl:33].S(=O)(=O)(O)O.N>>[OH2:10].[NH2:1][C:2]1[C:7]2[CH2:8][C:9]([CH3:11])([CH3:12])[O:10][C:6]=2[C:5]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][C:25](=[O:26])[CH3:30])[CH2:18][C@H:17]2[O:31][CH3:32])=[O:14])=[CH:4][C:3]=1[Cl:33].[NH2:1][C:2]1[C:7]2[CH2:8][C:9]([CH3:11])([CH3:12])[O:10][C:6]=2[C:5]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][C:25](=[O:26])[CH3:30])[CH2:18][C@H:17]2[O:31][CH3:32])=[O:14])=[CH:4][C:3]=1[Cl:33]

Participants

4

Reactant 3

HCID 222AmmoniaHCID 1118Sulfuric AcidHCID 67712855cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-[3-(2-methyl-1,3-dioxolan-2-yl)propyl]-4-piperidinyl]2,2-dimethyl-7-benzofurancarboxamide

Product 1

HCID 131718804cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-(4-oxopentyl)4-piperidinyl]-2,2-dimethyl-7-benzofurancarboxamide hemihydrateYield 51.6%

Procedure

A mixture of 5.4 parts of cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-[3-(2-methyl-1,3-dioxolan-2-yl)propyl]-4-piperidinyl]-2,2-dimethyl-7-benzofurancarboxamide and 85 ml of an aqueous sulfuric acid solution 1% was stirred for 2 hours at reflux temperature. After cooling, the reaction mixture was basified with ammonia and extracted with dichloromethane (2x). The combined extracts were dried, filtered and evaporated. The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 95:5). The eluent of the desired fraction was evaporated and the residue was suspended in 2,2'-oxybispropane. The product was filtered off and dried, yielding 2.4 parts (51.6%) of cis-4-amino-5-chloro-2,3-dihydro-N-[3-methoxy-1-(4-oxopentyl)-4-piperidinyl]-2,2-dimethyl-7-benzofurancarboxamide hemihydrate; mp. 137.7° C. (comp. 112).

Workup

  1. temperatureat reflux temperature
  2. temperatureAfter cooling
  3. extractionextracted with dichloromethane (2x)
  4. customThe combined extracts were dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 95:5)
  8. customThe eluent of the desired fraction was evaporated
  9. filtrationThe product was filtered off
  10. customdried

Sources & evidence

ORD record
ord-5c21092dea684e48a5db4baa9db84116
Source dataset
uspto-grants-1998_04
Patent number
US05739134

Reaction notes

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