Methanol → Benzyl 4-[((3R)-1-{3-[4-(methylsulfonyl)phenyl]propyl}piperidin-3-yl)methyl]piperazine-1-carboxylate

HRID 603162Notes

Reaction equation

HRID 603162 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][CH2:13]O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.I([O-])(=O)(=O)=O.[NH:42]1[CH2:47][CH2:46][CH2:45][C@@H:44]([CH2:48][N:49]2[CH2:54][CH2:53][N:52]([C:55]([O:57][CH2:58][C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=3)=[O:56])[CH2:51][CH2:50]2)[CH2:43]1.CO>C(Cl)Cl.S([O-])([O-])(=O)=O.[Mg+2]>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([CH2:11][CH2:12][CH2:13][N:42]2[CH2:47][CH2:46][CH2:45][C@@H:44]([CH2:48][N:49]3[CH2:50][CH2:51][N:52]([C:55]([O:57][CH2:58][C:59]4[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=4)=[O:56])[CH2:53][CH2:54]3)[CH2:43]2)=[CH:9][CH:10]=1)(=[O:3])=[O:4]

Participants

7

Reactant 4

HCID 887MethanolHCID 59846067Benzyl 4-[(3R)-piperidin-3-ylmethyl]piperazine-1-carboxylateHCID 67220797Benzenepropanol, 4-(methylsulfonyl)-HCID 131723735Dess-Martin Periodate

Product 1

HCID 57656816Benzyl 4-[((3R)-1-{3-[4-(methylsulfonyl)phenyl]propyl}piperidin-3-yl)methyl]piperazine-1-carboxylateYield 85.2%

Reagents, catalysts & solvents 2

HCID 24083Sulfuric acid magnesium salt (1:1)CatalystHCID 6344DichloromethaneSolvent2×

Procedure

3-[4-(Methylsulfonyl)phenyl]propan-1-ol (4.02 g, 18.8 mmol) and Dess-Martin periodate (8.49 g, 20.0 mmol) were stirred in DCM (50 ml) at room temperature overnight. The reaction was washed with NaOH solution (1N, 3×25 ml). Sodium triacetoxyborohydide (5.28 g, 25 mmol) was added to the mixture followed by benzyl 4-[(3R)-piperidin-3-ylmethyl]piperazine-1-carboxylate (3.97 g, 12.5 mmol) and magnesium sulphate (20.0 mg). The reaction was stirred at room temperature overnight then washed with water (20 ml) and dried using a phase separation cartridge. Silica was added and the solvent removed under reduced pressure to provide a cake which was added to the top of a silica column. Flash column chromatography (silica, 1%-10% MeOH:DCM) gave the title compound as a yellow oil (5.47 g, 85%).

Workup

  1. washThe reaction was washed with NaOH solution (1N, 3×25 ml)
  2. additionSodium triacetoxyborohydide (5.28 g, 25 mmol) was added to the mixture
  3. washthen washed with water (20 ml)
  4. customdried
  5. customa phase separation cartridge
  6. additionSilica was added
  7. customthe solvent removed under reduced pressure
  8. customto provide a cake which
  9. additionwas added to the top of a silica column

Sources & evidence

ORD record
ord-d0fa8fb2b68e4dcdb4d074a26f94d5d0
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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