Phthalylglycine aldehyde → HCID 69482477, compound

HRID 2364334Notes

Reaction equation

HRID 2364334 reaction equation
[NH2:1][C:2]1[C:3]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:4][CH:5]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[CH:7]=1.[O:21]=[C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](=[O:31])[N:23]1[CH2:32][CH:33]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[O:21]=[C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](=[O:31])[N:23]1[CH2:32][CH2:33][NH:1][C:2]1[C:3]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:4][CH:5]=[C:6]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 76201Phthalylglycine aldehyde2×HCID 5049666Sodium triacetoxyborohydride2×HCID 42637772Ethyl 3-amino-5-(4-fluorobenzyl)picolinate

Product 1

HCID 69482477HCID 69482477, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Conditions

Temperature
45 °C

Procedure

A solution of ethyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (1.50 g, 5.47 mmol) and (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetaldehyde (2.27 g, 12 mmol) under nitrogen in glacial acetic acid (50 mL) was treated with sodium triacetoxyborohydride (2.56 g, 12.1 mmol) at ambient temperature. After stirring for 30 min., 40 mL of glacial acetic acid (40 mL) was added, to dilute the reaction, followed by 0.17 g of (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)acetaldehyde and 0.45 g sodium triacetoxyborohydride. After stirring another 2½ h, the reaction was heated to 45° C. for another hour. The reaction was evaporated in vacuo and the residue was triturated with water (500 mL), filtered, and washed with water. The resulting solid was dissolved in CH2Cl2 dried over MgSO4, filtered and evaporated in vacuo. The residue was dissolved in CH2Cl2 and chromatographed on silica gel eluting with 0-50% EtOAc in hexanes to provide the product as an solid. 1H NMR (400 MHz, DMSO-D6) δ ppm 1.2 (t, J=7.1 Hz, 3 H), 3.5 (q, J=6.2 Hz, 2 H), 3.8 (t, J=6.0 Hz, 2 H), 3.9 (s, 2 H), 4.2 (q, J=7.0 Hz, 2 H), 7.1 (ddd, J=9.1, 6.9, 1.8 Hz, 2 H), 7.3 (m, 3 H), 7.6 (t, J=6.2 Hz, 1 H), 7.7 (d, J=1.6 Hz, 1 H), 7.8 (m, 4 H); ES+MS: 447 (M+H+).

Workup

  1. additionto dilute
  2. customthe reaction
  3. stirringAfter stirring another 2½ h
  4. customThe reaction was evaporated in vacuo
  5. customthe residue was triturated with water (500 mL)
  6. filtrationfiltered
  7. washwashed with water
  8. dissolutionThe resulting solid was dissolved in CH2Cl2
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. dissolutionThe residue was dissolved in CH2Cl2
  13. customchromatographed on silica gel eluting with 0-50% EtOAc in hexanes

Sources & evidence

ORD record
ord-38e48da09d5b43b3a72342902839150d
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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