Hydrochloric Acid → HCID 18180288, compound

HRID 1359020Notes

Reaction equation

HRID 1359020 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[C:5]([O:12][CH3:13])[C:4]=1[O-:14].[K+].Br[CH2:17][CH2:18][OH:19].CN(P(N(C)C)N(C)C)C.Cl>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[C:5]([O:12][CH3:13])[C:4]=1[O:14][CH2:17][CH2:18][OH:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 108982-BromoethanolHCID 15355Hexamethylphosphorous triamideHCID 22326798HCID 22326798, compound

Product 1

HCID 18180288HCID 18180288, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A slurry of potassium 2,6-dimethoxy-4-nitrophenolate [Collins, R. P. and Davis, M. J. Chem. Soc. (1961), 1986] (38 g, 160 mmol) in DMF (600 ml) was treated with 2-bromoethanol (25 ml, 353 mmol) and hexamethylphosphorus triamide (31 ml, 176 mmol) and the reaction heated at 115° for 6 h. After cooling, the reaction was poured onto 1M hydrochloric acid (1.5 l) and extracted with ethyl acetate (5×500 ml). The organics were washed with 1M sodium hydroxide (4×700 ml), brine (200 ml) and drfied (MgSO4). Concentration in vacuo gave 3,5-dimethoxy-4-(2-hydroxyethoxy)nitrobenzene as an off white solid (31 g) δH (CDCl3) 7.52 (2H, s), 4.21 (2H, t, J 2.9 Hz), 3.94 (3H, s), 3.76 (2H, m) and 2.94 (1H, br s). MS (ES+) 266 (MNa+, 50%), 244 (MH+, 100%). A mixture of this nitrobenzene (750 mg, 3.16 mmol) and 10% palladium on carbon (75 mg) in ethanol (50 ml) was degassed and then subjected to an atmosphere of hydrogen (balloon) for 16 h. at 200. Dichloromethane was added and the solution filtered and solvent removed in vacuo to give 3,5-dimethoxy-4-(2-hydroxyethoxy)aniline as a grey solid (620 mg) after trituration with diethyl ether. δH (CDCl3+DMSO) 5.84 (2H, s), 3.87-3.84 (2H, m), 3.64 (6H, s) and 3.52-3.49 (2H, m). MS (ES+) 214 (MH+, 100%.

Workup

  1. temperaturethe reaction heated at 115° for 6 h
  2. temperatureAfter cooling
  3. extractionextracted with ethyl acetate (5×500 ml)
  4. washThe organics were washed with 1M sodium hydroxide (4×700 ml), brine (200 ml)
  5. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-1545bf1d11c349b4897918c69e7b4ce8
Source dataset
uspto-grants-2003_07
Patent number
US06599908B1

Reaction notes

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