Dichloromethane → rac-(1R,2R)-2-(methylamino)cyclohexan-1-ol

HRID 1294584Notes

Reaction equation

HRID 1294584 reaction equation
[OH-].[Na+].ClCCl.C(O)(=O)[C@@H](C1C=CC=CC=1)O.[CH3:17][NH:18][C@@H:19]1[CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]1[OH:25]>O.[Cl-].[Na+].O>[CH3:17][NH:18][C@@H:19]1[CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]1[OH:25]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 131726521(1r, 2r)-2-Methylamino cyclohexanol (r)-mandelic acid salt

Product 1

HCID 12847193rac-(1R,2R)-2-(methylamino)cyclohexan-1-olYield 97.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

NaOH (108 g, 2.69 mol) was dissolved in water (350 ml). Brine (400 ml) was added and cooled to room temperature. Dichloromethane (300 ml) and (1R, 2R)-2-methylamino cyclohexanol (R)-mandelic acid salt (151.5 g, 538 mmol) were added and the mixture was stirred vigorously for 10 min. The layers were separated and the aqueous layer was again extracted with dichloromethane (3×200 ml). (separation of the layers is a time consuming process). The combined dichloromethane layers were dried (Na2SO4) and concentrated to give an oil (67.7 g, 97% yield). This oil was combined with two other batches of 2.3 g and 6.4 g (both with e.e.=99+%) and purified by Kugelrohr distillation (p=0.5 mbar, T=80-90° C.) giving a colorless oil (72.0 g, 92%) with 94% purity according to GC. This oil was again Kugelrohr distilled (p=0.3 mbar) giving two product containing fractions:

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was again extracted with dichloromethane (3×200 ml)
  3. custom(separation of the layers
  4. customconsuming process)
  5. dry with materialThe combined dichloromethane layers were dried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-0995a492aee34744b35775fd16da17fa
Source dataset
uspto-grants-2007_07
Patent number
US07241770B2

Reaction notes

Loading…