Sodium borohydride → 1-(4-{4-[2(S),3-dihydroxy-propoxy]-3-methylphenyl}-4-[4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]piperidin-1-yl)ethanone

HRID 250184Notes

Reaction equation

HRID 250184 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][C:7]([C:23]2[CH:36]=[CH:35][C:26]([O:27][CH2:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])=[C:25]([CH3:37])[CH:24]=2)([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH:18]([OH:21])[CH2:19][OH:20])=[C:12]([CH3:22])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[BH4-].[Na+]>CO>[OH:21][C@@H:18]([CH2:19][OH:20])[CH2:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:7]2([C:23]3[CH:36]=[CH:35][C:26]([O:27][CH2:28][CH:29]([OH:34])[C:30]([CH3:31])([CH3:32])[CH3:33])=[C:25]([CH3:37])[CH:24]=3)[CH2:6][CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8]2)=[CH:11][C:12]=1[CH3:22]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 668910911-(4-(1-Acetyl-4-[4-(2,3-dihydroxypropoxy)-3-methylphenyl]-piperidin-4-yl}-2-methylphenoxy)-3,3-dimethylbutan-2-one

Product 1

HCID 668894711-(4-{4-[2(S),3-dihydroxy-propoxy]-3-methylphenyl}-4-[4-(2-hydroxy-3,3-dimethylbutoxy)-3-methylphenyl]piperidin-1-yl)ethanoneYield 73%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-(4-{1-acetyl-4-[4-(2,3-dihydroxypropoxy)-3-methylphenyl]-piperidin-4-yl}-2-methylphenoxy)-3,3-dimethylbutan-2-one (0.14 g, 0.28 mmol) in anhyd MeOH (3 mL) cooled to 0° C. was added sodium borohydride (11 mg, 0.29 mmol). After 8 h the reaction was quenched with water and extracted with EtOAc (2×20 mL). The combined extracts were washed with brine, dried (anhyd Na2SO4), concentrated under reduced pressure and purified by reverse-phase HPLC (C18 column), eluting with 0.05% TFA in MeCN—H2O (1:9 to 9:1) to provide the title compound (0.10 g, 73%) as a white solid: 1H-NMR (CDCl3) δ 6.96-7.01 (4H, m), 6.74 (2H, d, J=8.3), 4.05-4.14 (2H, m), 4.03 (2H, m), 3.82-3.88 (2H, m), 3.74-3.80 (1H, dd, J=5.3, 11.4), 3.67-3.71 (1H, dd, J=2.8, 8.6), 3.64 (2H, m), 3.47 (2H, m), 2.27-2.36 (4H, m), 2.19 (3H, s), 2.18 (3H, s), 2.08 (3H, s), 1.00 (9H, s).

Workup

  1. customAfter 8 h the reaction was quenched with water
  2. extractionextracted with EtOAc (2×20 mL)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (anhyd Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. custompurified by reverse-phase HPLC (C18 column)
  7. washeluting with 0.05% TFA in MeCN—H2O (1:9 to 9:1)

Sources & evidence

ORD record
ord-d6aeadf8f4b446889d23eab1c6c33f1a
Source dataset
uspto-grants-2011_01
Patent number
US07863298B2

Reaction notes

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