Acetic Acid → HCID 68008713, compound

HRID 533160Notes

Reaction equation

HRID 533160 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.C[O:10][C:11]([C:13]1[C:18]([CH2:19][CH:20]=O)=[CH:17][C:16]([CH2:22][O:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:15][N:14]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C(Cl)Cl>[F:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[C:11](=[O:10])[C:13]3[N:14]=[CH:15][C:16]([CH2:22][O:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:17][C:18]=3[CH2:19][CH2:20]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 97314-FluoroanilineHCID 5049666Sodium triacetoxyborohydrideHCID 86667504HCID 86667504, compound

Product 1

HCID 68008713HCID 68008713, compoundYield 15.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4-Fluoroaniline (0.032 mL, 0.34 mmol) was added to a stirred solution of 3-(2-oxo-ethyl)-5-phenoxymethyl-pyridine-2-carboxylic acid methyl ester (80 mg, 0.28 mmol, from step 7) in DCM (4 mL). The mixture was stirred at RT for 1 h. Sodium triacetoxyborohydride (89 mg, 0.42 mmol) was added and the mixture was stirred at RT for 16 h. Acetic acid (0.040 mL) was added and the mixture was stirred at RT for additional 20 h. The mixture was diluted with DCM and washed with a saturated solution of NaHCO3 and brine. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; 7N solution of ammonia in methanol in DCM 0/100 to 4/96). The desired fractions were collected and the solvents evaporated in vacuo to yield an impure fraction which was re-purified by RP-HPLC on (C18 XBridge, 19×100, 5 μm; 80%/0.1% NH4CO3H/NH4OH pH 9 solution in water, 20% CH3CN to 0%/0.1% NH4CO3H/NH4OH pH 9 solution in water, 100% CH3CN), to yield 7-(4-fluoro-phenyl)-3-phenoxymethyl-6,7-dihydro-[1,7]-naphthyridin-8(5H)-one (14.86 mg, 15% yield) as a white solid: 1H NMR (500 MHz, CDCl3) δ 3.22 (t, J=6.4, 2 H), 4.01 (t, J=6.4, 2 H), 5.17 (s, 2 H), 6.98 (d, J=7.8, 2 H), 7.01 (t, J=7.5, 1 H), 7.07-7.16 (m, 2 H), 7.29-7.35 (m, 2 H), 7.36-7.42 (m, 2 H), 7.76 (br. s, 1 H), 8.78 (d, J=1.7, 1 H); LC-MS (M+H)=349.1.

Workup

  1. stirringthe mixture was stirred at RT for 16 h
  2. stirringthe mixture was stirred at RT for additional 20 h
  3. washwashed with a saturated solution of NaHCO3 and brine
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvents evaporated in vacuo
  8. customThe crude product was purified by flash column chromatography (silica; 7N solution of ammonia in methanol in DCM 0/100 to 4/96)
  9. customThe desired fractions were collected
  10. customthe solvents evaporated in vacuo
  11. customto yield an impure fraction which
  12. customwas re-purified by RP-HPLC on (C18 XBridge, 19×100, 5 μm; 80%/0.1% NH4CO3H/NH4OH pH 9 solution in water, 20% CH3CN to 0%/0.1% NH4CO3H/NH4OH pH 9 solution in water, 100% CH3CN)

Sources & evidence

ORD record
ord-9f772a942cb243edb89cd07deb3d58e6
Source dataset
uspto-grants-2014_10
Patent number
US08853237B2

Reaction notes

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