509-74-0 Usage
Originator
Acetylmethadol ,National Inst. for
Drug Abuse
Uses
Analgesic (narcotic).
Manufacturing Process
Racemic 1-dimethylamino-2-propanol (100.0 g, 0.97 mol) was stirred with
vinyl propionate (63.6 ml, 0.58 mol) at 40°C and Novozym 435 (5.0 g) was
added. The reaction was stirred slowly for 75 h and after this time TLC (10%
methanol/dichloromethane-visualize KMnO4 solution) indicated that the
reaction had gone to at least 50% conversion. The enzyme was removed by
filtration and the filtrate was distilled at reduced pressure. S-(+)-1-
Dimethylamino-2-propanol was obtained as a colourless oil (31.6 g, 64%),
boil point 35°C.
A solution of thionyl chloride (37 ml, 0.48 mol) in chloroform (20 ml) was
added slowly, with stirring, to a cooled (ice/water) solution of S-(+)-1-
dimethylamino-2-propanol (30.6 g, 0.32 mol) in chloroform (85 ml). When the
addition was complete a precipitate formed. The mixture was allowed to warm
to room temperature over 30 min and then heated to reflux for a further 30
min. The precipitate redissolved on heating but then the product crystallized
out from the boiling solvent as it formed. More chloroform (20 ml) was
needed to maintain the stirring. The cooled mixture was diluted with ether
and filtered. The 45.0 g (96%) of crude product was isolated. This was
recrystallised from 2-propanol as in the other series to give 30.9 g (65%) of
R-(-)-1-dimethylamino-2-chloropropane, melting point 192°-193°C.
A 50% w/v solution of sodium hydroxide in water (12.5 ml, 0.32 mol) was
added to a mechanically stirred suspension of diphenylacetonitrile (15.0
g,0.08 mol) and dibenzo-18-crown-6 (0.5 g, cat.) in dimethylsulphoxide (12.5
ml). The color rapidly deepened to an orange/brown. R-(-)-1-Dimethylamino-
2-chloropropane (30.0 g, 0.095 mol) was added in portions over 30 min, this
caused the temperature to rise to 30°C. After the addition was complete the
mixture was warmed to 45°-50°C (water bath) and stirred for a further hour.
The reaction mixture was then allowed to cool to room temperature and was
poured into ice/water (250 ml) and extracted with ethyl acetate (3 times 150
ml). The combined extracts were dried (MgSO4) and filtered and evaporated
down to -100 ml. The product was extracted into 1N HCl (100 ml+50 ml) and
this was back washed with ethyl acetate. The aqueous was basified with 2 M
sodium hydroxide and extracted into ethyl acetate (3 times 100 ml). The
extracts were washed with brine (70 ml), dried (MgSO4), and evaporated
down to a yellow oil. This was chilled and triturated with cold hexane (50 ml)
to give a white solid which was collected by filtration and washed thoroughly
with a further portion of cold hexane (100 ml). 14.65 g (33%) of S-(+)-2,2-
diphenyl-4-dimethylaminopentanenitrile were obtained, melting point 100°-
101°C (recrystallised from hexane).
All apparatus was dried and the reaction was carried out under an inert
atmosphere of argon. A solution of S-(+)-2,2-diphenyl-4-
dimethylaminopentanenitrile (10.0 g, 0.018 mol) in toluene (15 ml) was
added to a stirred solution of 3 M ethyl magnesium bromide in ether (10.7 ml,
0.03 mol). The ether was removed under reduced pressure and the remaining
solution heated at reflux (135°-140°C) for 3 h. The solution went slightly
cloudy but there was no significant precipitation. After cooling to room
temperature 2 N HCl (30 ml) was added with care and then stirring was continued at 135°-140°C for a further 30 min. The two phases were allowed
to separate and cool to room temperature. After scratching the sides of the
flask a solid started to crystallise from the aqueous phase. The flask was
cooled to complete crystallisation and the white solid was collected by
filtration. This solid was recrystallised from water to yield 6.6 g (53%) of S-
(+)-methadone hydrochloride (6-dimethylamino-4,4-diphenyl-3-heptanone
hydrochloride) were obtained, melting point 240°-241°C.
S-(+)-Methadone hydrochloride (600.0 mg,1.74 mmol) was dissolved in
ethanol (10 ml) and the solution was stirred whilst sodium borohydride (3.47
mmol) was added portion-wise over a period of 5 min. When the addition was
complete a spatula end of cerium (III) chloride heptahydrate was added. The
resultant solution was allowed to stir at room temperature for 30 min then the
ethanol was removed under reduced pressure. The residue was portioned
between diethyl ether (40 ml) and water (40 ml). The aqueous layer was
extracted with more diethyl ether (2 times 20 ml) and then the combined
organics were washed with brine (40 ml) and dried (MgSO4). The ether was
removed under reduced pressure to leave 435.0 mg, (80%) of 6-
dimethylamino-4,4-diphenyl-3-heptanol.
6-Dimethylamino-4,4-diphenyl-3-heptanol (435.0 mg, 1.40 mmol) dissolved in
ethyl acetate (10 ml) was treated with acetyl chloride (183.0 mg, 2.33 mmol).
The mixture was refluxed for 2 h. After allowing the solution to cool to room
temperature the solvent was removed under reduced pressure to leave a
white foam, this crystallised from ethyl acetate to give 6-dimethylamino-4,4-
diphenyl-3-acetoxyheptane hydrochloride (levo-α-acetyl methadol
hydrochloride) (420.0 mg, 79%).
The 6-dimethylamino-4,4-diphenyl-3-acetoxyheptane may be produced by
treatment of the 6-dimethylamino-4,4-diphenyl-3-acetoxyheptane
hydrochloride with sodium hydroxide.
Therapeutic Function
Narcotic analgesic
Check Digit Verification of cas no
The CAS Registry Mumber 509-74-0 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,0 and 9 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 509-74:
(5*5)+(4*0)+(3*9)+(2*7)+(1*4)=70
70 % 10 = 0
So 509-74-0 is a valid CAS Registry Number.
InChI:InChI=1/C23H31NO2/c1-6-22(26-19(3)25)23(17-18(2)24(4)5,20-13-9-7-10-14-20)21-15-11-8-12-16-21/h7-16,18,22H,6,17H2,1-5H3
509-74-0Relevant articles and documents
Process for the preparation of optically active methadones in high enantiomeric purity
-
, (2008/06/13)
PCT No. PCT/GB97/01441 Sec. 371 Date Apr. 9, 1999 Sec. 102(e) Date Apr. 9, 1999 PCT Filed May 27, 1997 PCT Pub. No. WO97/45551 PCT Pub. Date Dec. 4, 1997A method of preparing optically active methadones comprises an enzymatic process for the resolution of 1-dialkyl-amino-2-propanol and conversion of the enantiomers to the optically active methadones in high enantiomeric purity.
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