Acetic Acid → HCID 9817445, compound

HRID 399540Notes

Reaction equation

HRID 399540 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:12][C:11]2[CH2:10][CH:9]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[CH2:8][CH2:7][C:6]=2[NH:5][C:4]1=O.C(O)(=O)C.Cl>C1COCC1>[OH:1][CH2:2][CH:3]1[CH2:12][CH:11]2[CH:6]([CH2:7][CH2:8][CH:9]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[CH2:10]2)[NH:5][CH2:4]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 18967712HCID 18967712, compound

Product 1

HCID 9817445HCID 9817445, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3,4,5,6,7,8-Hexahydro-3-hydroxymethyl-6-((4-methoxyphenyl)methyl)quinolin-2[1H]-one (24.7 g) (prepared according to step c) in THF (200 ml) was treated with borane-dimethylsulphide complex (25 ml) and stirred at room temperature under argon for 18 hours. The reaction mixture was then treated with aqueous acetic acid (20%) until pH 5 and then stirred for an hour. HCl was added until the mixture was strongly acidic and then the solvent removed in vacuo. The residue was dissolved in methanol, concentrated to remove borate esters then converted to the hydrochloride salt (28 g). This salt was recrystallised from ethyl acetate-methanol (200 ml-15 ml) to yield a fraction (15.7 g) containing 34% of the title compound. This fraction was triturated with ethyl acetate, converted to the free base and fractionally crystallised from t-butylmethyl ether, yielding a fraction containing 84% of the title compound. Further recrystallisation was carried out from t-butylmethyl ether diethylether (1:1) and the product converted to the hydrochloride salt (1.8 g), mp 288°-289.5° C.

Workup

  1. stirringstirred for an hour
  2. customthe solvent removed in vacuo
  3. dissolutionThe residue was dissolved in methanol
  4. concentrationconcentrated
  5. customto remove borate esters
  6. customThis salt was recrystallised from ethyl acetate-methanol (200 ml-15 ml)
  7. customto yield a fraction (15.7 g)

Sources & evidence

ORD record
ord-bcf6db2b875b4a8db440a535c261c0a5
Source dataset
uspto-grants-1998_10
Patent number
US05821251

Reaction notes

Loading…