3-Pyridinemethanol → 4-((((Pyridin-3-ylmethoxy)carbonyl)amino)methyl)benzoic acid

HRID 1942811Notes

Reaction equation

HRID 1942811 reaction equation
C1N=CN([C:6]([N:8]2C=N[CH:10]=[CH:9]2)=[O:7])C=1.[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][OH:20])[CH:14]=1.NCC1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=1.CCN(CC)CC.C1CCN2C(=NCCC2)CC1>C1COCC1>[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][O:20][C:6]([NH:8][CH2:9][C:10]2[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=2)=[O:7])[CH:14]=1

Participants

7

Reactant 5

HCID 75103-PyridinemethanolHCID 8471TriethylamineHCID 655264-(Aminomethyl)Benzoic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene

Product 1

HCID 98173384-((((Pyridin-3-ylmethoxy)carbonyl)amino)methyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of CDI (107 g, 662 mmol) in dry THF (700 mL) was treated with a solution of pyridin-3-ylmethanol (72.2 g, 662 mmol) in THF (300 mL) dropwise over 10 minutes. The resulting solution was stirred for 1.25 hours and then added dropwise over 15 minutes to a water bath cooled suspension of 4-(aminomethyl)benzoic acid (100 g, 662 mmol), Et3N (92 mL, 662 mmol) and DBU (100 mL, 662 mmol) in dry THF (1400 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue suspended in water (2500 mL), cooled in an ice-water bath and the pH adjusted to 5 with 6 N HCl (˜300 mL). The precipitate was collected by filtration, washed with cold MeOH and dried to give 4-[({[(pyridin-3-ylmethyl)oxy]carbonyl}amino)methyl]benzoic acid as a white solid. 1H NMR (d6-DMSO, 600 MHz) δ 12.82 (br s, 1H), 8.56 (d, J=1.8 Hz, 1H), 8.51 (dd, J=4.8 and 1.8 Hz, 1H), 7.93 (t, J=6.3 Hz, 1H), 7.87 (d, J=8.4 Hz, 2H), 7.76 (t, J=8.4 Hz, 1H), 7.38 (dd, J=7.2 and 4.8 Hz, 1H), 7.33 (d, J=8.4 Hz, 2H), 5.07 (s, 2H), 4.25 (d, J=6.3 Hz, 1H).

Workup

  1. additionadded dropwise over 15 minutes to a water bath
  2. temperaturecooled
  3. stirringThe reaction mixture was stirred at room temperature overnight
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. temperaturecooled in an ice-water bath
  6. filtrationThe precipitate was collected by filtration
  7. washwashed with cold MeOH
  8. customdried

Sources & evidence

ORD record
ord-7a62b7d4f4004f39a8b18015cd84da27
Source dataset
uspto-grants-2013_03
Patent number
US08389553B2

Reaction notes

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