Ammonium Chloride → HCID 15728750, compound

HRID 256908Notes

Reaction equation

HRID 256908 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([O:16][CH:17]([O:19][CH2:20][CH3:21])[CH3:18])[C:9]1[S:10][CH:11]=[CH:12][C:13]=1[CH:14]=[O:15].[CH3:22][N:23]1[CH2:28][CH2:27][CH:26]([Mg]Cl)[CH2:25][CH2:24]1.CN1CCC(Cl)CC1.[Cl-].[NH4+]>CCOCC.O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([O:16][CH:17]([O:19][CH2:20][CH3:21])[CH3:18])[C:9]1[S:10][CH:11]=[CH:12][C:13]=1[CH:14]([CH:26]1[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]1)[OH:15]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 793424-chloro-N-methylpiperidineHCID 15728749HCID 15728749, compoundHCID 178480358HCID 178480358, compound

Product 1

HCID 15728750HCID 15728750, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a stirred solution of the 2-[(2-fluorophenyl)(1-(ethoxy)ethoxy)methyl]-3-thiophenecarboxaldehyde and tetrahydrofuran (400 ml), cooled to -78° C. under nitrogen, was added, via syringe, N-methyl-4-piperidinylmagnesium chloride over 1.5 hrs. (the Grignard reagent was prepared from N-methyl-4-chloropiperidine (29.4 g) according to the procedure of J. T. Strupczewski, et al., et al., J. Med. Chem., 28, 761 (1985), followed by dilution with tetrahydrofuran (45 ml)). The solution was allowed to warm slowly to -20° C. over 2.5 hrs, and dilute aqueous ammonium chloride solution and ether were added. The layers were separated and the organic layer washed with water. The combined aqueous layers were back-extracted with ether, and the combined organic layers washed with brine, dried over anhydrous potassium carbonate, filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 0-45% methanol/dichloromethane) to afford 6.4 g (20% overall) of α-[2-[2-fluorophenyl(1-(ethoxy)ethoxy)methyl]-3-thienyl]-1-methyl-4-piperidinemethanol.

Workup

  1. additionwas added, via syringe
  2. customThe layers were separated
  3. washthe organic layer washed with water
  4. extractionThe combined aqueous layers were back-extracted with ether
  5. washthe combined organic layers washed with brine
  6. dry with materialdried over anhydrous potassium carbonate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography (silica gel, 0-45% methanol/dichloromethane)

Sources & evidence

ORD record
ord-cd0fda6997a645678fb0f6fc6463d90a
Source dataset
uspto-grants-1993_11
Patent number
US05260319

Reaction notes

Loading…