L-Alaninol → Tert-Butyl 4-[2-[3-fluoro-4-((R)-2-hydroxy-1-methylethyl-carbamoyl)phenoxymethyl]pyridin-5-yl]piperidine-1-carboxylate

HRID 42149

Reaction equation

HRID 42149 reaction equation
[C:1]([C:4]1[CH:30]=[CH:29][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)=[CH:12][N:11]=2)=[CH:6][C:5]=1[F:31])(O)=[O:2].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:55][C@@H:56]([CH3:59])[CH2:57][OH:58].C(=O)([O-])O.[Na+]>O1CCCC1>[F:31][C:5]1[CH:6]=[C:7]([CH:29]=[CH:30][C:4]=1[C:1](=[O:2])[NH:55][C@H:56]([CH3:59])[CH2:57][OH:58])[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:18][CH2:17]2)=[CH:12][N:11]=1

Participants

7

Reactant 5

HCID 80307L-AlaninolHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67083327Tert-Butyl 4-[2-(4-carboxy-3-fluorophenoxymethyl)pyridin-5-yl]piperidine-1-carboxylate

Product 1

HCID 86654262Tert-Butyl 4-[2-[3-fluoro-4-((R)-2-hydroxy-1-methylethyl-carbamoyl)phenoxymethyl]pyridin-5-yl]piperidine-1-carboxylateYield 87.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of tert-butyl 4-[2-(4-carboxy-3-fluorophenoxymethyl)pyridin-5-yl]piperidine-1-carboxylate (Example 10) (21 mg, 0.049 mmol), 1-hydroxybenzotriazole monohydrate (9.3 mg, 0.061 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (12 mg, 0.061 mmol) in dry tetrahydrofuran (0.5 mL) was stirred at room temperature for 1 hour followed by the addition of a solution of (S)-(−)-2-amino-1-propanol (7.6 μL, 0.098 mmol) in dry tetrahydrofuran (0.05 mL). The mixture was stirred at room temperature overnight, to which was added saturated aqueous sodium hydrogen carbonate solution and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/1) to give the title compound as a white crystal (21 mg, yield 86%).

Workup

  1. extractionextracted with chloroform
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (chloroform/methanol=100/1)

Sources & evidence

ORD record
ord-09601bab574c4bba8afd367d1b7dbbbe
Source dataset
uspto-grants-2013_09
Patent number
US08536176B2

Linked notes

Loading…