Ammonium Chloride → HCID 69354327, compound

HRID 2186357Notes

Reaction equation

HRID 2186357 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[OH:11][CH:12]([C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[C:40]([O:43][CH3:44])[CH:41]=2)[N:36]=[CH:35][CH:34]=1)[CH2:13][CH2:14][C@@H:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]#[C:23][C:24]2[S:25][CH:26]=[CH:27][CH:28]=2)[CH2:17][C@@H:16]1[C:29](OC)=[O:30].[Cl-].[NH4+]>C1(C)C=CC=CC=1.ClCCl>[OH:30][CH2:29][C@@H:16]1[C@H:15]([CH2:14][CH2:13][CH:12]([OH:11])[C:33]2[C:42]3[C:37](=[CH:38][CH:39]=[C:40]([O:43][CH3:44])[CH:41]=3)[N:36]=[CH:35][CH:34]=2)[CH2:20][CH2:19][N:18]([CH2:21][C:22]#[C:23][C:24]2[S:25][CH:26]=[CH:27][CH:28]=2)[CH2:17]1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 21225700DiisobutylaluminumhydrideHCID 131723272HCID 131723272, compound

Product 1

HCID 69354327HCID 69354327, compoundYield 36.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

4.2 cm3 of a 20% solution of diisobutylaluminum hydride in toluene were added to a mixture, cooled to −20° C., with stirring, of 0.5 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(thien-2-yl)prop-2-ynyl]piperidine-3-carboxylate in 10 cm3 of toluene. Stirring was maintained for 3 hours at this temperature and then 15 cm3 of a saturated ammonium chloride solution were added, stirring was maintained for 15 minutes and the temperature was allowed to rise to a temperature in the region of 20° C. The aqueous phase was separated by settling, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure (2 kPa). The residue obtained was purified by chromatography on a column of silica gel (particle size 20-45 μm; diameter 2 cm; height 20 cm), elution was carried out, under a pressure of 50 kPa of nitrogen, with dichloromethane and then a mixture of dichloromethane and methanol (95/5 by volume), and 30-cm3 fractions were collected. Fractions 14 to 16 were combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was taken up in 5 cm3 of dichloromethane and filtered. The filtrate was concentrated to dryness under reduced pressure (2 kPa). 0.17 g of (3R,4R)-3-hydroxymethyl-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(thien-2-yl)prop-2-ynyl]piperidine was obtained in the form of a gum.

Workup

  1. temperaturewas maintained for 3 hours at this temperature
  2. stirringstirring
  3. temperaturewas maintained for 15 minutes
  4. customto rise to a temperature in the region of 20° C
  5. customThe aqueous phase was separated
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (2 kPa)
  9. customThe residue obtained
  10. customwas purified by chromatography on a column of silica gel (particle size 20-45 μm; diameter 2 cm; height 20 cm), elution
  11. additiona mixture of dichloromethane and methanol (95/5 by volume), and 30-cm3 fractions
  12. customwere collected
  13. customevaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  14. customThe residue obtained
  15. filtrationfiltered
  16. concentrationThe filtrate was concentrated to dryness under reduced pressure (2 kPa)

Sources & evidence

ORD record
ord-345f84320c9e4f9598376eea80afdba7
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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