Sodium hydride → Rac-(3R*,4R*)-tert-butyl 4-(((2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylate

HRID 571976Notes

Reaction equation

HRID 571976 reaction equation
[OH:1][CH:2]1[CH:7]([CH2:8]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:6][CH2:5][N:4]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:3]1.[O:27]1[C:36]2[CH:35]=[C:34]([NH:37]C(=O)OC(C)(C)C)[N:33]=[CH:32][C:31]=2[O:30][CH2:29][CH2:28]1.[H-].[Na+].C([O-])(O)=O.[Na+]>CN(C=O)C>[O:27]1[C:36]2[CH:35]=[C:34]([NH:37][CH2:8][CH:7]3[CH2:6][CH2:5][N:4]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:3][CH:2]3[OH:1])[N:33]=[CH:32][C:31]=2[O:30][CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 516892Sodium BicarbonateHCID 57458140tert-Butyl 3-hydroxy-4-((tosyloxy)methyl)piperidine-1-carboxylateHCID 67351669(2,3-Dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-carbamic acid tert-butyl ester

Product 1

HCID 117641835Rac-(3R*,4R*)-tert-butyl 4-(((2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)amino)methyl)-3-hydroxypiperidine-1-carboxylateYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of rac-(3R*,4R*)-tert-butyl 3-hydroxy-4-((tosyloxy)methyl)piperidine-1-carboxylate (prepared as described in Tetrahedron (2008), 64, 2456-2464, 0.26 g, 0.67 mmol) and tert-butyl (2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)carbamate (prepared as described in WO 2009/104159, 0.17 g, 0.67 mmol, 1 eq.) was dissolved in DMF (2.5 mL). NaH (60% dispersion in oil, 0.04 g, 0.88 mmol, 1.3 eq.) was added and the mixture was vigorously stirred at rt for 2 h. More NaH (0.03 g, 0.67 mmol, 1 eq.) was added. After two more hours, sat. aq. NaHCO3 (5 mL) was added and the mixture was extracted with EA (3×10 mL). The combined org. phases were dried over MgSO4 and concentrated under reduced pressure. The residue was purified by CC (DCM/MeOH 19:1) to afford the title compound as a white solid (0.15 g, 62% yield).

Workup

  1. extractionthe mixture was extracted with EA (3×10 mL)
  2. dry with materialphases were dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by CC (DCM/MeOH 19:1)

Sources & evidence

ORD record
ord-49ed53d4880343bb942c51d391733bd3
Source dataset
uspto-grants-2015_05
Patent number
US09029368B2

Reaction notes

Loading…