Acetic Acid → (3R,4R)-4-(4-Bromo-2-nitro-phenylamino)-1-methyl-piperidin-3-ol

HRID 1670632Notes

Reaction equation

HRID 1670632 reaction equation
C=O.Cl.[Br:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C@@H:12]2[CH2:17][CH2:16][NH:15][CH2:14][C@H:13]2[OH:18])=[C:7]([N+:19]([O-:21])=[O:20])[CH:6]=1.[C:22](O)(=O)C.C([BH3-])#N.[Na+]>O>[Br:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C@@H:12]2[CH2:17][CH2:16][N:15]([CH3:22])[CH2:14][C@H:13]2[OH:18])=[C:7]([N+:19]([O-:21])=[O:20])[CH:6]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 67334527HCID 67334527, compound

Product 1

HCID 67334708(3R,4R)-4-(4-Bromo-2-nitro-phenylamino)-1-methyl-piperidin-3-olYield 97%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Add formaldehyde (20.5 mL, 37-41% aqueous solution) to a solution of (3R,4R)-4-(4-bromo-2-nitro-phenylamino)-piperidin-3-ol.hydrochloride salt (0.0.024 mol, 8.68 g) and acetic acid (10.2 mL) in water (42 mL) and stir the reaction mixture at room temperature for 30 min. Add sodium cyanoborohydride (0.073 mol, 4.6 g) and stir the reaction mixture for 3 h. Quench the reaction mixture with sodium bicarbonate solution and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate to obtain the title compound (7.8 g, 97%). 1H NMR (400 MHz, CDCl3) δ 1.63-1.71 (m, 1H), 2.16-2.21 (m, 2H), 2.33 (s, 3H), 2.35-2.38 (m, 1H), 2.60 (br s, 1H), 2.80 (d, 1H), 3.54-3.56 (m, 1H), 3.75-3.79 (m, 1H), 6.92 (d, 1H), 7.48 (dd, 1H), 8.14 (d, 1H), 8.30 (d, 1H).

Workup

  1. customQuench the reaction mixture with sodium bicarbonate solution
  2. extractionextract with dichloromethane
  3. dry with materialDry the organic layer over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate

Sources & evidence

ORD record
ord-6eb42c0856d049e1bdb7fea96cfa16ea
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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