Hydrochloric Acid → HCID 18008061, compound

HRID 2117224Notes

Reaction equation

HRID 2117224 reaction equation
[C:1]([N:4]([CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=1)[CH2:5][CH2:6][CH2:7][CH2:8][O:9][CH2:10][C:11]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:12]=1[C:13]([O:15]C)=[O:14])(=[O:3])[CH3:2].[OH-].[Na+].Cl.O>C(O)C>[C:1]([N:4]([CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=1)[CH2:5][CH2:6][CH2:7][CH2:8][O:9][CH2:10][C:11]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:12]=1[C:13]([OH:15])=[O:14])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 962WaterHCID 14798Sodium HydroxideHCID 18008044HCID 18008044, compound

Product 1

HCID 18008061HCID 18008061, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

Methyl 2-[4-(acetyl-quinolin-2-ylmethyl-amino)-butoxymethyl]-6-methyl-benzoate (375 mg, 0.86 mmol, EXAMPLE 40a) is dissolved in ethanol (7.5 mL). 10 N NaOH (860 μL, 8.6 mmol) is added, and the contents are heated to 90° C. overnight. The reaction is cooled to r.t. and 2 N HCl (4.3 mL) is added, followed by dropwise addition of 2 N HCl to adjust the pH to ˜4-6. The contents are poured into water (100 mL) and extracted with dichloromethane (3×75 mL). The organic fractions are pooled and washed with brine (3×100 mL), dried over MgSO4, filtered and reduced under vacuum to dryness. The crude material is purified by flash chromatography (silica, 6% methanol in dichloromethane) to give the title compound. 1H NMR (300 MHz, CDCl3) Rotamers 2:1 δ 8.37 (d, 0.5H), 8.28-8.15 (m, 1.5H), 7.88-7.83 (m, 1.25H), 7.80-7.73 (m, 1.75H), 7.65-7.57 (m, 1.25H), 7.43 (d, 0.25H), 7.33-7.10 (m, 3H), 5.24 (s, 1.33H), 5.01 (s, 0.66H), 4.67 (s, 1.33H), 4.63 (s, 0.66H), 3.55-3.45 (m, 2.66), 3.39-3.32 (m, 1.33), 2.58 (s, 2H), 2.55 (s, 1H), 2.31 (s, 1H), 1.95-1.82 (m, 2H), 1.77-1.62 (m, 2H). MS (ESI) 421 (M+H)+.

Workup

  1. temperatureThe reaction is cooled to r.t.
  2. extractionextracted with dichloromethane (3×75 mL)
  3. washwashed with brine (3×100 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customThe crude material is purified by flash chromatography (silica, 6% methanol in dichloromethane)

Sources & evidence

ORD record
ord-f7b64975343c49fea19c959d782bcd85
Source dataset
uspto-grants-2008_10
Patent number
USRE040558E1

Reaction notes

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