Sodium Bicarbonate → 4-(3'-Fluoro-5'-hydroxymethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-ylideneaminooxy)-piperidine-1-carboxylic acid isopropyl ester

HRID 2066864Notes

Reaction equation

HRID 2066864 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][N:14]=[C:15]2[CH2:20][CH2:19][N:18]([C:21]3[C:26]([F:27])=[CH:25][C:24]([CH:28]=[O:29])=[CH:23][N:22]=3)[CH2:17][CH2:16]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[BH4-].[Na+].C([O-])(O)=O.[Na+]>CO>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][N:14]=[C:15]2[CH2:16][CH2:17][N:18]([C:21]3[C:26]([F:27])=[CH:25][C:24]([CH2:28][OH:29])=[CH:23][N:22]=3)[CH2:19][CH2:20]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 866550114-(3'-Fluoro-5'-formyl-2,3,5,6-tetrahydro-[1,2]bipyridinyl-4-ylideneaminooxy)-piperidine-1-carboxylic acid isopropyl ester

Product 1

HCID 583336054-(3'-Fluoro-5'-hydroxymethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-ylideneaminooxy)-piperidine-1-carboxylic acid isopropyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The crude 53b was taken up with methanol (10 mL), cooled in an ice bath and treated with NaBH4 (0.52 g, 13.7 mmol). The mixture was stirred for 2 h and treated with aqueous NaHCO3 (10 mL). The mixture was extracted with 40 mL of ethyl acetate, washed with brine (3×30 mL) and concentrated under vacuum. The residue was purified by flash chromatography (eluent: 20 to 70% ethyl acetate+0.1% triethylamine in hexane) to afford 296 mg (44% yield) of 53-1: LC-MS 409.2 (MH+), tR=5.59 (Method 2). EC50: 224 nM.

Workup

  1. temperaturecooled in an ice bath
  2. extractionThe mixture was extracted with 40 mL of ethyl acetate
  3. washwashed with brine (3×30 mL)
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by flash chromatography (eluent: 20 to 70% ethyl acetate+0.1% triethylamine in hexane)

Sources & evidence

ORD record
ord-d5a097b7b29e4a918f30c72914af670f
Source dataset
uspto-grants-2012_10
Patent number
US08293729B2

Reaction notes

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