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

HRID 1670636Notes

Reaction equation

HRID 1670636 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 131729090HCID 131729090, compound

Product 1

HCID 67336014(3S,4S)-4-(4-Bromo-2-nitro-phenylamino)-1-methyl-piperidin-3-olYield 92%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Add formaldehyde (24 mL, 37-41% aqueous solution) to a solution of (3S,4S)-4-(4-bromo-2-nitro-phenylamino)-piperidin-3-ol, hydrochloride (0.028 mol, 9.8 g) and acetic acid (12 mL) in water (46 mL) and stir the reaction mixture at room temperature for 30 min. Add sodium cyanoborohydride (0.083 mol, 5.26 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 (8.4 g, 92%). 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-652897e7dc0245a0b2aeaa34a2e8f32e
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

Loading…