Dichloromethane → (1S)-1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine

HRID 918929Notes

Reaction equation

HRID 918929 reaction equation
C(N[C@H](C(O)=O)CC(C)C)(=O)C.[CH2:13]([O:15][C:16]1[CH:17]=[C:18]([C@H:24]([NH2:30])[CH2:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[CH3:14].ClCCl.[OH-].[Na+]>O>[CH2:13]([O:15][C:16]1[CH:17]=[C:18]([C@H:24]([NH2:30])[CH2:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[CH3:14]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 66648136L-Leucine, N-acetyl-, compd. with (alphaS)-3-ethoxy-4-methoxy-alpha-((methylsulfonyl)methyl)benzenemethanamine (1:1)

Product 1

HCID 11282264(1S)-1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamineYield 95%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
20 °C

Procedure

After a mixture of (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine N-acetyl-L-Leucine salt (1.10 kg, 2.46 moles), deionizer water (4.40 L), and dichloromethane (DCM, 5.50 L) was charged into a reaction vessel, a solution of sodium hydroxide (196.0 g, 4.90 moles) in 1.00 L of deionizer water was charged into the reaction vessel over about 5 minutes at 15-25° C. The resulting mixture was stirred for at least 10 minutes at 15-25° C. and then the aqueous and organic phases were allowed to separate. The pH of the upper aqueous phase was maintained or adjusted at pH 13-14. The phases were separated and the upper aqueous phase was extracted with DCM (2×4.4 L). The pH of the aqueous phase was maintained at 13-14 throughout the extractions. The DCM extracts were combined and washed with deionizer water (3.3 L) until the pH of the aqueous phase reached 11 or less. DCM was removed under vacuum below 35° C. The water content of the residual solid should be <0.1% w/was measured by Karl Fisher titration. The residual solid was dried azeotropically with more DCM. The solid was dried to a constant weight in vacuo at 30-35° C. to give (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl-ethylamine as a white powder (639.0-672.0 g, 95-100% yield).

Workup

  1. additionwas charged into a reaction vessel
  2. customto separate
  3. temperatureThe pH of the upper aqueous phase was maintained
  4. customThe phases were separated
  5. extractionthe upper aqueous phase was extracted with DCM (2×4.4 L)
  6. temperatureThe pH of the aqueous phase was maintained at 13-14 throughout the extractions
  7. washwashed with deionizer water (3.3 L) until the pH of the aqueous phase
  8. customDCM was removed under vacuum below 35° C
  9. dry with materialThe residual solid was dried azeotropically with more DCM
  10. customThe solid was dried to a constant weight in vacuo at 30-35° C.

Sources & evidence

ORD record
ord-cf6ce6bf212e4b6e823563a3d672626f
Source dataset
uspto-grants-2016_03
Patent number
US09272035B2

Reaction notes

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