Sodium borohydride → (4-Chloro-2,5-dimethoxyphenyl)methanol

HRID 1754026Notes

Reaction equation

HRID 1754026 reaction equation
[Cl:1][C:2]1[C:9]([O:10][CH3:11])=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.[BH4-].[Na+]>C(O)C>[Cl:1][C:2]1[C:9]([O:10][CH3:11])=[CH:8][C:5]([CH2:6][OH:7])=[C:4]([O:12][CH3:13])[CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 110089594-Chloro-2,5-dimethoxybenzaldehyde

Product 1

HCID 68287683(4-Chloro-2,5-dimethoxyphenyl)methanolYield 96%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of 4-chloro-2,5-dimethoxybenzaldehyde (29.0 g, 145 mmol, 1 equiv) in absolute ethanol (550 mL) was added sodium borohydride (27.3 g, 723 mmol, 5 equiv). The reaction was allowed to stir at room temperature for 6 h and slowly quenched via dropwise addition of acetone. The reaction mixture was diluted with EtOAc, washed with brine (×2), dried (MgSO4), filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography on SiO2 (EtOAc/hexanes, 1:1) to give 28.0 g (96% yield) of 2 as a white solid: Mp 89-90° C.; Rf 0.53 (EtOAc/hexanes, 1:1); IR (neat) 3258, 2958, 2915, 1495, 1461, 1392, 1204, 1061, 719 cm−1; 1H NMR (300 MHz, CDCl3) δ 6.90 (s, 1 H), 6.80 (s, 1 H), 4.55 (d, 2 H, J=4.2 Hz), 3.77 (s, 3H), 3.71 (s, 3 H), 3.10 (bs, 1 H); 13C NMR (75 MHz, CDCl3) δ 150.6, 148.7, 128.4, 120.8, 112.5, 112.4, 60.3, 56.5, 55.6; HRMS (ESI+) m/z calcd for C9H12O3Cl 203.0475, found 203.0465.

Workup

  1. customslowly quenched via dropwise addition of acetone
  2. additionThe reaction mixture was diluted with EtOAc
  3. washwashed with brine (×2)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by chromatography on SiO2 (EtOAc/hexanes, 1:1)

Sources & evidence

ORD record
ord-381905612d8b46a394cb93a6d0f81bba
Source dataset
uspto-grants-2015_10
Patent number
US09169182B2

Reaction notes

Loading…