Hydrochloric Acid → (2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride

HRID 1992776Notes

Reaction equation

HRID 1992776 reaction equation
B(O)(O)[C@H]1N(C([C@@H](N)C(C)C)=O)CCC1.CS(O)(=O)=O.[CH3:21][N:22]([CH3:38])[CH2:23][C@H:24]([CH3:37])[C@@:25]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=1)([OH:28])[CH2:26][CH3:27].CN(C)C[C@H](C)[C@](C1C=CC=C(OC)C=1)(O)CC.[ClH:57]>CC(C)=O.O>[ClH:57].[CH3:38][N:22]([CH3:21])[CH2:23][C@H:24]([CH3:37])[C@@:25]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH3:36])[CH:30]=1)([OH:28])[CH2:26][CH3:27]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid4×HCID 9942979(alphaR)-alpha-[(1S)-2-(Dimethylamino)-1-methylethyl]-alpha-ethyl-3-methoxybenzenemethanolHCID 11522448Talabostat mesylateHCID 11708619(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol

Product 1

HCID 67043376(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

A 100 l double wall jacketed reaction vessel with electric impeller stirrer, gas transfer line, Pt100 temperature sensor and oil-based cooling and heating system was charged with 15 kg (59.7 mol) of a mixture of the enantiomeric pair (2R,3R)/(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (70%) and the enantiomeric pair (2R,3S)/(2S,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol (30%) in 70 l of acetone at 20° C. and a stirrer speed of 100 rpm The solution was cooled to 5° C. Within 20 min, approx. 2.0 kg of gaseous hydrogen chloride were passed over the solution, the temperature in the vessel rising continuously to 28° C. despite cooling. The hydrogen chloride was taken from a hydrogen chloride cylinder which was connected to the gas transfer line of the vessel through a pressure reduction valve and hose and was placed on a balance for weight measurement. Further gaseous hydrogen chloride was then passed over until a 5 ml sample of the solution diluted with 10 ml of water had a pH value of 1-3. The solution was stirred at 5° C. for 2 h. The suspension was then centrifuged off in a centrifuge and washed once with 10 l of acetone. The product was dried in a drying cabinet at 40° C. for 24 h under reduced pressure to a final pressure of 20 mbar. 11.16 kg (65% of theoretical) of the enantiomeric pair (2R,3R)/(2S,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride were obtained as a colourless product. The residual content of the undesired enantiomeric pair (2S,3R)/(2R,3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride was 3%.

Workup

  1. temperatureheating system
  2. customrising continuously to 28° C.
  3. temperaturedespite cooling
  4. customwas connected to the gas transfer line of the vessel through a pressure reduction valve
  5. washwashed once with 10 l of acetone
  6. customThe product was dried in a drying cabinet at 40° C. for 24 h under reduced pressure to a final pressure of 20 mbar

Sources & evidence

ORD record
ord-079b9b6eaffe478594213f55ac5543f6
Source dataset
uspto-grants-2010_01
Patent number
US07649114B2

Reaction notes

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