Methanol → {4-[(R)-2-(3-hydroxy-4-phenyl-butyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester

HRID 349367Notes

Reaction equation

HRID 349367 reaction equation
[BH4-].[Na+].CO.[CH3:5][O:6][C:7](=[O:32])[CH2:8][O:9][CH2:10][C:11]#[C:12][CH2:13][N:14]1[C@@H:19]([CH2:20][CH2:21][C:22](=[O:30])[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:18][CH2:17][CH2:16][C:15]1=[O:31]>C(Cl)Cl>[CH3:5][O:6][C:7](=[O:32])[CH2:8][O:9][CH2:10][C:11]#[C:12][CH2:13][N:14]1[C:15](=[O:31])[CH2:16][CH2:17][CH2:18][C@@H:19]1[CH2:20][CH2:21][CH:22]([OH:30])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[OH:6][CH2:7][CH2:8][O:9][CH2:10][C:11]#[C:12][CH2:13][N:14]1[C@@H:19]([CH2:20][CH2:21][CH:22]([OH:30])[CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:18][CH2:17][CH2:16][C:15]1=[O:31]

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 69022436{4-[(R)-2-Oxo-6-(3-oxo-4-phenyl-butyl)-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester

Product 2

HCID 69021200(R)-1-[4-(2-hydroxy-ethoxy)-but-2-ynyl]-6-(3-hydroxy-4-phenyl-butyl)-piperidin-2-oneYield 14%HCID 69021369{4-[(R)-2-(3-hydroxy-4-phenyl-butyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Sodium borohydride (4.4 mg, 0.12 mmol) followed by MeOH (0.2 mL) was added to a solution of {4-[(R)-2-oxo-6-(3-oxo-4-phenyl-butyl)-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester (15 mg, 0.039 mmol) in CH2Cl2 (0.6 mL) at 0° C. After 5 min at 0° C. the reaction was quenched with aqueous HCl (0.2 M, 5 mL). The reaction mixture was extracted with CH2Cl2 (3×5 mL), then the combined extracts were dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→5% MeOH/CH2Cl2) afforded 13 mg (86%) of {4-[(R)-2-(3-hydroxy-4-phenyl-butyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester and 2 mg (14%) of (R)-1-[4-(2-hydroxy-ethoxy)-but-2-ynyl]-6-(3-hydroxy-4-phenyl-butyl)-piperidin-2-one.

Workup

  1. customAfter 5 min at 0° C. the reaction was quenched with aqueous HCl (0.2 M, 5 mL)
  2. extractionThe reaction mixture was extracted with CH2Cl2 (3×5 mL)
  3. dry with materialthe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ae72aa619ae74890b67d6cd5fcada134
Source dataset
uspto-grants-2007_02
Patent number
US07179820B2

Reaction notes

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