Triethylamine → 3,5-Dihydroxybenzoic Acid

HRID 2407600Notes

Reaction equation

HRID 2407600 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].C(N(CC)CC)C.[CH:13]([O:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([O:26][CH:27]([CH3:29])[CH3:28])[CH:25]=1)[C:20](Cl)=[O:21])([CH3:15])[CH3:14]>ClCCl>[CH:13]([O:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([O:26][CH:27]([CH3:29])[CH3:28])[CH:25]=1)[C:20]([N:3]([O:4][CH3:5])[CH3:2])=[O:21])([CH3:15])[CH3:14].[OH:26][C:24]1[CH:23]=[C:19]([CH:18]=[C:17]([OH:16])[CH:25]=1)[C:20]([OH:21])=[O:4]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 189253473,5-Diisopropoxybenzoyl chloride

Product 2

HCID 74243,5-Dihydroxybenzoic AcidHCID 582610093,5-diisopropoxy-N-methoxy-N-methylbenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diisopropoxybenzoic acid (compound F, 10 g, 41 mmol) was dissolved in benzene (100 mL) in a 500 mL round bottom flask. Thionyl chloride (12.2 mL, 168 mmol) was added and the reaction heated at reflux for 1 hour. The mixture was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was redissolved in dichloromethane and concentrated again to give 3,5-diisopropoxybenzoyl chloride. In a separate 200 mL flask, N,O-dimethylhydroxylamine-HCl (4.0 g, 42 mmol) was suspended in 80 mL dichloromethane at 0° C. Triethylamine (12.4 mL, 88 mmol) was added slowly, followed by crude 3,5-diisopropoxybenzoyl chloride. The reaction flask was allowed to warm to ambient temperature and stirred overnight. The reaction was quenched with water and extracted with three portions of dichloromethane. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the resulting brown oil by column chromatography (30% acetone/hexane) gave the Weinreb amide (compound G) as a yellow oil in 60% yield from 3,5-dihydroxybenzoic acid: Rf 0.33 (30:70 acetone/hexane); IR (cm−1): 2977, 1647, 1590, 1441, 1374, 1184, 1155, 1113, 1037, 964; 1H NMR (250 MHz, C6D6): δ 1.06 (dd, J=2.5, 5.9 Hz, 12H), 3.00 (s, 3H), 3.05 (s, 3H), 4.19 (qn, J=6.2 Hz, 2H), 6.69 (t, J=2.5 Hz, 1H), 7.10 (d, J=2.5 Hz, 2H); 13C NMR (63 MHz, C6D6): 21.9 (4C), 33.4, 60.4, 69.8 (2C), 106.6, 108.1 (2C), 137.0, 159.3 (2C), 169.8.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with three portions of dichloromethane
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the resulting brown oil by column chromatography (30% acetone/hexane)

Sources & evidence

ORD record
ord-ada93c160a484d48857476bcb0017aa4
Source dataset
uspto-grants-2014_08
Patent number
US08809563B2

Reaction notes

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