Lansoprazole → Dexlansoprazole

HRID 1661137Notes

Reaction equation

HRID 1661137 reaction equation
[CH3:1][C:2]1[C:3]([O:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:4][CH:5]=[N:6][C:7]=1[CH2:8][S+:9]([O-:19])[C:10]1[NH:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=2[N:18]=1.CCCCCC.C(N(CC)CC)C.CCCCCC.CC(O)C>CC(O)C>[CH3:1][C:2]1[C:7]([CH2:8][S@:9]([C:10]2[NH:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[N:18]=2)=[O:19])=[N:6][CH:5]=[CH:4][C:3]=1[O:20][CH2:21][C:22]([F:25])([F:23])[F:24]

Participants

6

Reactant 4

HCID 3883LansoprazoleHCID 8058HexaneHCID 8471TriethylamineHCID 21585144Isopropanol hexane

Product 1

HCID 9578005DexlansoprazoleYield 27.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Lansoprazole (racemate) (34.2 g) was dissolved in 2-propanol (1,710 ml) and hexane (1,140 ml) containing triethylamine (0.2%) and fractionated by HPLC (column: CHIRALCEL OD 50 mm dia.×500 mm, temperature: room temperature, mobile phase: hexane/2-propanol=85/15, flow rate: 60 ml/min, detection wavelength: 285 nm, 1 shot: about 300 mg) to isolate the individual optical isomers. Fractions of an optical isomer of shorter retention time were combined and concentrated; the individual lots were combined and dissolved in ethanol (250 ml); after triethylamine (3 ml) was added, the solution was filtered through a 0.45 μm filter. After the filtrate was concentrated, hexane was added, and the filtrate was again evaporated to dryness to yield R(+)-lansoprazole (9.31 g, optical purity 98.3% ee) as an amorphous substance.

Workup

  1. customto isolate the individual optical isomers
  2. concentrationconcentrated
  3. dissolutiondissolved in ethanol (250 ml)
  4. additionafter triethylamine (3 ml) was added
  5. filtrationthe solution was filtered through a 0.45 μm
  6. filtrationfilter
  7. concentrationAfter the filtrate was concentrated
  8. additionhexane was added
  9. customthe filtrate was again evaporated to dryness

Sources & evidence

ORD record
ord-d4d0a67ad53a4df1a7b35256b40dc675
Source dataset
uspto-grants-2011_10
Patent number
US08030333B2

Reaction notes

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