Iodine → HCID 19377149, compound

HRID 2211337Notes

Reaction equation

HRID 2211337 reaction equation
[Mg].II.[Cl:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][C:6]=1[Cl:12].[O:13]=[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]([N:24]([CH3:28])[C:25](=[O:27])[CH3:26])[CH2:16][CH2:15]1.S(=O)(=O)(O)O>C(OCC)C.O1CCCC1>[Cl:12][C:6]1[CH:7]=[C:8]([C:14]2([OH:13])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]([N:24]([CH3:28])[C:25](=[O:27])[CH3:26])[CH2:16][CH2:15]2)[CH:9]=[CH:10][C:5]=1[Cl:4]

Participants

8

Reactant 5

HCID 807IodineHCID 1118Sulfuric AcidHCID 88591Benzene, 1,2-dichloro-4-iodo-HCID 5462224MagnesiumHCID 19377152HCID 19377152, compound

Product 1

HCID 19377149HCID 19377149, compoundYield 49.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

Magnesium turnings (2.04 g) and a crystal of iodine were stirred in dry diethyl ether (24 ml) as a solution of 1,2-dichloro-4-iodobenzene (23.17 g) in dry diethyl ether (60 ml) was added over 15 minutes. The mixture was stirred for 15 minutes and refluxed for a further 15 minutes to complete formation of the Grignard reagent. The mixture was cooled to room temperature and a solution of N-(1,2,3,4-tetrahydro-4-keto-1-naphthyl)-N-methylacetamide (12.3 g) in dry tetrahydrofuran (134 ml ) was added over 5 mutes. The mixture was stirred for 4 hours at room temperature, heated under reflux for 30 minutes, cooled and treated with 4N aqueous sulphuric acid (30 ml). The lower aqueous phase was separated and discarded, dichloromethane was added, and the solution was washed with water (2×25 ml). The organic layer was evaporated under vacuum to give a mixture of racemic cis-(1R*, 4S*)- and trans-(1R*, 4R*)-isomers (ratio 87:13 respectively by nmr spectroscopy techniques) as a light brown gum (24.5 g) which was stirred with diethyl ether (150 ml) for 1 hour, then filtered, to give the title compound as cream crystals (10.2 g, 49.5%), m.p. 146°-148° C.; Rf 0.41 (silica; chloroform, methanol; 95:5). Found: C,62.96; H,5.24; N,4.00 C19H19Cl2NO2 requires C,62.65; H,5.26; N 3.85%. GLC assay on a 2.1 m×4 mm 3% OV-17 column, temperature programmed from 100° to 275° C. at 10° C./minute, showed the product to be 96% pure (retention time 41.5 minutes) containing 3% recovered ketone.

Workup

  1. additionwas added over 15 minutes
  2. temperaturerefluxed for a further 15 minutes
  3. stirringThe mixture was stirred for 4 hours at room temperature
  4. temperatureheated
  5. temperatureunder reflux for 30 minutes
  6. temperaturecooled
  7. customThe lower aqueous phase was separated
  8. additiondichloromethane was added
  9. washthe solution was washed with water (2×25 ml)
  10. customThe organic layer was evaporated under vacuum
  11. customto give
  12. filtrationfiltered

Sources & evidence

ORD record
ord-345c54c95dad4b0d841ae46ecc482518
Source dataset
uspto-grants-1995_10
Patent number
US05463126

Reaction notes

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