Water → [7-Chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]-methanol

HRID 2415731Notes

Reaction equation

HRID 2415731 reaction equation
O.C[O:3][C:4]([C:6]1[C:7]([Cl:28])=[N:8][C:9]2[CH:10]=[C:11]3[O:27][CH2:26][CH2:25][O:24][C:12]3=[CH:13][C:14]=2[C:15]=1[CH2:16][N:17]1[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]1)=O.[H-].C([Al+]CC(C)C)C(C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C(Cl)Cl>[Cl:28][C:7]1[C:6]([CH2:4][OH:3])=[C:15]([CH2:16][N:17]2[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22]2)[C:14]2[CH:13]=[C:12]3[O:24][CH2:25][CH2:26][O:27][C:11]3=[CH:10][C:9]=2[N:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 9357Potassium Sodium TartrateHCID 154504617-Chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester2×HCID 21225700Diisobutylaluminumhydride

Product 1

HCID 22637071[7-Chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]-methanol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 4-necked 5-L round-bottom flask is equipped with an overhead mechanical stirrer, a water-cooled condenser and nitrogen flow is maintained. The flask is charged with 7-chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro[1,4]dioxino [2,3-g]quinoline-8-carboxylic acid methyl ester (Intermediate 7, 194 g, 495 mol), as a solution in 1 L of methylene chloride. To the solution is added 1 M diisobutylaluminum hydride in methylene chloride (2.00 L, 2.00 mol) over, 15 min. The solution is healed to reflux during the addition. The reaction is allowed to cool to ambient temperature and stirred for 4 h. The reaction mixture is transferred to a 15-L separatory tunnel containing a saturated solution of Rochelle's salt (5 L). After being stirred for 2.5 h, the organic layer is separated and the aqueous layer is extracted with methylene chloride (3×2.5 L). The combined organic layers are washed with brine (3 L), dried over anhydrous sodium sulfate and concentrated in vacuo. The resultant thick brown slurry is successively treated with methylene chloride (500 mL) and hexane (1 L). The mixture is swirled at 0° C. for 30 min. The precipitate is collected on a Buchner funnel, washed with 1 liter of hexane and dried in vacuo. at 30° C. yielding [7-chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8yl]-methanol as a yellow crystalline solid: mp 178-180° C. 1H NMR (CDCl3, 200 MHz) d 2.26 (s, 3H), 2.63 (br. s, 4H), 4.00 (s, 2H). 4.39 (s, 4H), 4.93 (s, 2H), 6.10 (br. s, 1H), 7.46 (s, 1H), 7.51 (s, 1H). Elemental analysis: Calculated for C18H22ClN3O3: C 59.42, H 6.09, N 11.55. Found: C 59.41, H 6.12, N 11.46.

Workup

  1. customA 4-necked 5-L round-bottom flask is equipped with an overhead mechanical stirrer
  2. temperaturenitrogen flow is maintained
  3. temperatureto reflux during the addition
  4. stirringAfter being stirred for 2.5 h
  5. customthe organic layer is separated
  6. extractionthe aqueous layer is extracted with methylene chloride (3×2.5 L)
  7. washThe combined organic layers are washed with brine (3 L)
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. additionThe resultant thick brown slurry is successively treated with methylene chloride (500 mL) and hexane (1 L)
  11. waitThe mixture is swirled at 0° C. for 30 min
  12. customThe precipitate is collected on a Buchner funnel
  13. washwashed with 1 liter of hexane
  14. customdried in vacuo

Sources & evidence

ORD record
ord-cd7dabe6909d463ab209762ce7d0db1c
Source dataset
uspto-grants-2004_11
Patent number
US06821982B2

Reaction notes

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