Acetic Acid → HCID 86732809, compound

HRID 525940Notes

Reaction equation

HRID 525940 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([F:33])[C:9]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH:11]=2)[C:6](=[O:34])[C:5]([CH:35]=O)=[CH:4]1)[CH3:2].[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>ClCCCl>[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([F:33])[C:9]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH:11]=2)[C:6](=[O:34])[C:5]([CH2:35][N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 86732808HCID 86732808, compound

Product 1

HCID 86732809HCID 86732809, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 1-ethyl-5-fluoro-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carbaldehyde (18 g, 36.6 mmol) in 1,2-Dichloroethane (DCE) (100 mL) was added pyrrolidine (4.53 mL, 54.9 mmol), sodium triacetoxyborohydride (15.52 g, 73.2 mmol) and AcOH (0.105 mL, 1.831 mmol). The reaction mixture was stirred at 25° C. for 3 h. LCMS indicated completion of the reaction. The mixture was extracted with DCM and washed with brine. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude material was purified by normal phase automatic silica column chromatography (Combinflash RF), using a 40 g gold column and eluting with MeOH/DCM (0-20%). The product was further purified by reverse phase automatic chromatography (Combinflash RF), using a 150 g gold C18 column and eluting with acetonitrile/Water (0%-60%) to afford 1-ethyl-5-fluoro-6,7-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)quinolin-4(1H)-one (9.4 g, 17.20 mmol, 47.0% yield) as a pale yellow solid. LCMS: (M+H)+: 547.3.

Workup

  1. customcompletion of the reaction
  2. extractionThe mixture was extracted with DCM
  3. washwashed with brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by normal phase automatic silica column chromatography (Combinflash RF)
  7. washeluting with MeOH/DCM (0-20%)
  8. customThe product was further purified by reverse phase automatic chromatography (Combinflash RF)
  9. washeluting with acetonitrile/Water (0%-60%)

Sources & evidence

ORD record
ord-d786c852e14748439c5748a7e0f50cf0
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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