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

HRID 2052961Notes

Reaction equation

HRID 2052961 reaction equation
[BH4-].[Na+].CO.[CH3:5][O:6][C:7](=[O:33])[CH2:8][O:9][CH2:10][C:11]#[C:12][CH2:13][N:14]1[C:19](=[O:20])[CH2:18][CH2:17][CH2:16][C@@H:15]1/[CH:21]=[CH:22]/[C:23](=[O:32])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=1>C(Cl)Cl>[CH3:5][O:6][C:7](=[O:33])[CH2:8][O:9][CH2:10][C:11]#[C:12][CH2:13][N:14]1[C:19](=[O:20])[CH2:18][CH2:17][CH2:16][C@@H:15]1/[CH:21]=[CH:22]/[CH:23]([OH:32])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=1.[Cl:31][C:27]1[CH:26]=[C:25]([CH2:24][CH:23]([OH:32])/[CH:22]=[CH:21]/[C@@H:15]2[N:14]([CH2:13][C:12]#[C:11][CH2:10][O:9][CH2:8][CH2:7][OH:6])[C:19](=[O:20])[CH2:18][CH2:17][CH2:16]2)[CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 11212242(4-{(R)-2-[(E)-4-(3-Chlorophenyl)-3-oxo-but-1-enyl]-6-oxo-piperidin-1-yl}-but-2-ynyloxy)-acetic acid methyl ester

Product 2

HCID 11247138(4-{(R)-2-[(E)-4-(3-chlorophenyl)-3-hydroxy-but-1-enyl]-6-oxo-piperidin-1-yl}-but-2-ynyloxy)-acetic acid methyl esterYield 46%HCID 11440740(R)-6-[(E)-4-(3-chlorophenyl)-3-hydroxy-but-1-enyl]-1-[4-(2-hydroxyethoxy)-but-2-ynyl]-piperidin-2-oneYield 4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Sodium borohydride (5 mg, 0.13 mmol) followed by MeOH (0.5 mL) was added to a solution of (4-{(R)-2-[(E)-4-(3-chlorophenyl)-3-oxo-but-1-enyl]-6-oxo-piperidin-1-yl}-but-2-ynyloxy)-acetic acid methyl ester (48 mg, 0.11 mmol) in CH2Cl2 (1.0 mL) at 0° C. After 20 min at 0° C. the reaction was quenched with 0.5 N aqueous HCl. The reaction mixture was extracted with CH2Cl2 (3×10 mL), then the combined extracts were dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→2% MeOH/CH2Cl2) followed by preparative thin layer chromatography (5% MeOH/CH2Cl2) afforded 22 mg (46%) of (4-{(R)-2-[(E)-4-(3-chlorophenyl)-3-hydroxy-but-1-enyl]-6-oxo-piperidin-1-yl}-but-2-ynyloxy)-acetic acid methyl ester and 1.7 mg (4%) of (R)-6-[(E)-4-(3-chlorophenyl)-3-hydroxy-but-1-enyl]-1-[4-(2-hydroxyethoxy)-but-2-ynyl]-piperidin-2-one.

Workup

  1. customAfter 20 min at 0° C. the reaction was quenched with 0.5 N aqueous HCl
  2. extractionThe reaction mixture was extracted with CH2Cl2 (3×10 mL)
  3. dry with materialthe combined extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-23e8bac287384ed488a913146932000b
Source dataset
uspto-grants-2008_02
Patent number
US07326716B2

Reaction notes

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