Water → Methyl 2-amino-4-(hydroxymethyl)benzoate

HRID 1433104Notes

Reaction equation

HRID 1433104 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]([C:12](OC)=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Li+].[B-](CC)(CC)CC.O>C1COCC1>[NH2:1][C:2]1[CH:11]=[C:10]([CH2:12][OH:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

5

Reactant 3

HCID 962WaterHCID 79336Dimethyl aminoterephthalateHCID 23712863Lithium triethylborohydride

Product 1

HCID 602338Methyl 2-amino-4-(hydroxymethyl)benzoateYield 60.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 16.0 g (76.6 mmole) of dimethyl aminoterephthalate in 200 ml of anhydrous THF cooled to −78° C. is added 250 ml (250 mmole) of 1 M Super Hydride dropwise over 1 hour. The mixture is stirred for an additional 1.5 hours warming to 0° C. (a little starting material on TLC is observed). The mixture is poured into 300 ml of cold water and extracted with ethyl acetate. The organic layer is washed with water and the two layers are allowed to stand for 30 minutes. The organic layer is dried over MgSO4 and filtered. The filtrate is evaporated. The residue is dissolved in ethyl acetate and the solution is poured over a Buchner funnel containing silica gel, using 150 ml of ethyl acetate to wash the funnel. The filtrate is evaporated. The residue is dissolved in the minimum amount of ethyl acetate and the solution is diluted to the cloudy point with hexane. Additional hexane is added as the product precipitates. A total of 100 ml of hexane is added and the solid is collected and vacuum dried to give 8.4 g of the title intermediate material, 98-100° C. mp; 61% yield. 1H NMR (CDCl3, 300 MHz) δ 7.82 (d, 1H), 6.67 (s, 1H), 6.60 (d, 1H), 5.75 (bs, 2H), 4.62 (s, 2H), 3.86 (s, 3H), 1.83 (bs, 1H). EI MS, [M]+=181.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer is washed with water
  3. waitto stand for 30 minutes
  4. dry with materialThe organic layer is dried over MgSO4
  5. filtrationfiltered
  6. customThe filtrate is evaporated
  7. dissolutionThe residue is dissolved in ethyl acetate
  8. additionthe solution is poured over a Buchner funnel
  9. additioncontaining silica gel
  10. washto wash the funnel
  11. customThe filtrate is evaporated
  12. dissolutionThe residue is dissolved in the minimum amount of ethyl acetate
  13. additionthe solution is diluted to the cloudy point with hexane
  14. additionAdditional hexane is added as the product
  15. customprecipitates
  16. additionA total of 100 ml of hexane is added
  17. customthe solid is collected
  18. customvacuum dried

Sources & evidence

ORD record
ord-c8736e94806f4f0885b009b692b0593d
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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