Acetic Acid → 3-[(Ethyl-methyl-amino)-methyl]-5-methyl-benzoic acid

HRID 1958808Notes

Reaction equation

HRID 1958808 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([CH3:12])[CH:11]=1)[C:6]([OH:8])=[O:7])=O.CC(O)=O.[CH2:17]([NH:19][CH3:20])[CH3:18].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.CN1C(=O)CCC1>[CH2:17]([N:19]([CH2:1][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([CH3:12])[CH:11]=1)[C:6]([OH:8])=[O:7])[CH3:20])[CH3:18]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 12219N-MethylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 197881733-Formyl-5-methylbenzoic acid

Product 1

HCID 669323243-[(Ethyl-methyl-amino)-methyl]-5-methyl-benzoic acidYield 46.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 3-formyl-5-methyl-benzoic acid (2.83 g, 17.2 mmol) in DCM (100 mL) and NMP (15 mL), AcOH (3.17 g, 51.7 mmol) and N-ethyl-methylamine (4.08 g, 69.0 mmol) is added. The mixture is stirred at rt for 45 min before NaBH(OAc)3 (8.12 g, 34.5 mmol) is added. The mixture is stirred at rt for 16 h before it is concentrated. The remaining residue is dissolved in MeCN and DMF and filtered over a paper filter. The filtrate is separated by prep. HPLC (Waters XBridge 50×50 mm+100×50 mm, eluting with a gradient of acetonitrile in water containing 0.5% of sat. aq. ammonia) to give the title compound as a white solid (1.67 g). LC-MS*: tR=0.46 min, [M−H]−=206.28; 1H NMR (D6-DMSO): δ 1.03 (t, J=7.3 Hz, 3H), 2.09 (s, 3H), 2.35 (s, 3H), 2.39 (q, J=7.0 Hz, 2H), 3.46 (s, 2H), 7.31 (s, 1H), 7.63 (s, 1H), 7.67 (s, 1H).

Workup

  1. additionis added
  2. concentrationis concentrated
  3. dissolutionThe remaining residue is dissolved in MeCN
  4. filtrationDMF and filtered over a paper
  5. filtrationfilter
  6. customThe filtrate is separated by prep
  7. washHPLC (Waters XBridge 50×50 mm+100×50 mm, eluting with a gradient of acetonitrile in water containing 0.5% of sat. aq. ammonia)

Sources & evidence

ORD record
ord-15e81c78c61348ad9bd899d660330b30
Source dataset
uspto-grants-2013_04
Patent number
US08410151B2

Reaction notes

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