Methanesulfonic Acid → (2R)-2-phenylcarbonyloxypropyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate mesylate

HRID 1948758Notes

Reaction equation

HRID 1948758 reaction equation
C([O-])(O)=O.[Na+].Cl.[NH2:7][C@@H:8]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([OH:32])[CH:26]=1)[C:9]([O:11][CH2:12][C@H:13]([O:15][C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:17])[CH3:14])=[O:10].[CH3:33][S:34]([OH:37])(=[O:36])=[O:35].C(OCC)(=O)C>O>[S:34]([OH:37])(=[O:36])(=[O:35])[CH3:33].[NH2:7][C@@H:8]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([OH:32])[CH:26]=1)[C:9]([O:11][CH2:12][C@H:13]([O:15][C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:17])[CH3:14])=[O:10]

Participants

6

Reactant 4

HCID 6395Methanesulfonic Acid2×HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 11582017(2R)-2-Phenylcarbonyloxypropyl (2S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoate Hydrochloride

Product 1

HCID 16125134(2R)-2-phenylcarbonyloxypropyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate mesylateYield 99.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of NaHCO3 (9.87 g, 117.5 mmol) in water (80 mL) was slowly added to a solution of hydrochloride salt 1d (31.0 g, 78.3 mmol) in water (300 mL). The resulting aqueous suspension was extracted with ethyl acetate (EtOAc) (2×400 mL). The combined EtOAc extract was washed with water, then brine, and dried through MgSO4. Methanesulfonic acid (6.04 mL, 93.12 mmol) was slowly added to the ethyl acetate (EtOAc) solution while stirred. White precipitate formed as soon as the addition of methanesulfonic acid was complete. The suspension was stirred for another 30 min and then filtered. The filter cake was washed three times with ethyl acetate (EtOAc) and vacuum dried overnight to afford 35.4 g (quantitative yield) of anhydrous mesylate salt 1 as a white solid. 1H NMR (400 MHz, CD3OD): δ 1.40 (d, J=6.4 Hz, 3H), 2.70 (s, 3H), 2.98 (dd, J=7.8, 14.6 Hz, 1H), 3.10 (dd, J=5.6, 14.4 Hz, 1H), 4.24 (dd, J=5.8, 7.8 Hz, 1H), 4.38 (dd, J=6.8, 12.0 Hz, 1H), 4.52 (dd, J=3.4, 11.8 Hz, 1H), 5.40 (dp, J=3.2, 6.4 Hz, 1H), 6.52 (dd, J=2.2, 8.2 Hz, 1H), 6.67 (d, J=2.2 Hz, 1H), 6.69 (d, J=8.0 Hz, 1H), 7.47 (t, J=7.6 Hz, 2H), 7.60 (br t, J=7.4 Hz, 1H), 8.01 (d, J=7.6 Hz, 2H). MS (ESI) m/z 360.07 (M−H)+ and 358.01 (M−H)−.

Workup

  1. extractionThe resulting aqueous suspension was extracted with ethyl acetate (EtOAc) (2×400 mL)
  2. extractionThe combined EtOAc extract
  3. washwas washed with water
  4. dry with materialbrine, and dried through MgSO4
  5. customWhite precipitate
  6. customformed as
  7. stirringThe suspension was stirred for another 30 min
  8. filtrationfiltered
  9. washThe filter cake was washed three times with ethyl acetate (EtOAc) and vacuum
  10. customdried overnight

Sources & evidence

ORD record
ord-270cf9feaedc46ea971db3bb15572dbc
Source dataset
uspto-grants-2013_03
Patent number
US08399513B2

Reaction notes

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