7-(3-tert-Butoxycarbonyl-phenyl)-5,6,7,8-tetrahydro-[2,7]naphthyridine-4-carboxylic acid methyl ester → 3-[5-(methoxycarbonyl)-3,4-dihydro-2,7-naphthyridin-2(1H)-yl]benzoic acid

HRID 338771Notes

Reaction equation

HRID 338771 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:14]2[CH2:13][CH2:12][N:11]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([O:23]C(C)(C)C)=[O:22])[CH:16]=3)[CH2:10][C:9]=2[CH:8]=[N:7][CH:6]=1)=[O:4]>C(O)=O>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][CH:8]=[C:9]2[C:14]=1[CH2:13][CH2:12][N:11]([C:15]1[CH:16]=[C:17]([CH:18]=[CH:19][CH:20]=1)[C:21]([OH:23])=[O:22])[CH2:10]2)=[O:4]

Participants

3

Reactant 1

HCID 866958807-(3-tert-Butoxycarbonyl-phenyl)-5,6,7,8-tetrahydro-[2,7]naphthyridine-4-carboxylic acid methyl ester

Product 1

HCID 866958813-[5-(methoxycarbonyl)-3,4-dihydro-2,7-naphthyridin-2(1H)-yl]benzoic acidYield 66%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 7-(3-tert-Butoxycarbonyl-phenyl)-5,6,7,8-tetrahydro-[2,7]naphthyridine-4-carboxylic acid methyl ester (6.9 g, 0.0188 mol) and 98% formic acid (30 mL) was heated at 50° C. for 4 hr and at 30° C. overnight. HPLC analysis showed the reaction was not complete. It was heated at 50° C. for an additional 1.5 hr. The reaction mixture was concentrated under reduced pressure. Diluted with dichloromethane (200 mL) and cooled to 0° C. To the mixture (liquid and solid) was added saturated sodium bicarbonate until to get a pH=5-6 at 0° C. The solid was collected, washed with water (50 mL), dichloromethane (50 mL) and air dried. The solid was triturated with acetone (50 mL) for 30 min. The yellow-green solid was collected and dried in a drying pistol with refluxing acetone overnight to give the title compound (3.86 g, 66%). 1H NMR 300 MHz (d6-DMSO), δ 13 (brs, 1H), 8.8 (s, 1H), 8.65 (s, 1H), 7.5 (m, 4H), 4.5 (s, 2H), 3.8 (s, 3H), 3.6 (t, 2H), 3.2 (t, 2H).

Workup

  1. temperatureIt was heated at 50° C. for an additional 1.5 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionDiluted with dichloromethane (200 mL)
  4. temperaturecooled to 0° C
  5. additionTo the mixture (liquid and solid) was added saturated sodium bicarbonate until
  6. customto get a pH=5-6 at 0° C
  7. customThe solid was collected
  8. washwashed with water (50 mL), dichloromethane (50 mL) and air
  9. customdried
  10. customThe solid was triturated with acetone (50 mL) for 30 min
  11. customThe yellow-green solid was collected
  12. dry with materialdried in a drying pistol with refluxing acetone overnight

Sources & evidence

ORD record
ord-f896782e415e44798a4142d73465c34f
Source dataset
uspto-grants-2014_11
Patent number
US08889870B2

Reaction notes

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