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

HRID 229500

Reaction equation

HRID 229500 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([OH:27])[CH:21]=1)[C:4]([O:6][CH2:7][C@H:8]([O:10][C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:12])[CH3:9])=[O:5].C([O-])(O)=O.[Na+].[CH3:33][S:34]([OH:37])(=[O:36])=[O:35]>>[S:34]([OH:37])(=[O:36])(=[O:35])[CH3:33].[NH2:2][C@@H:3]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([OH:27])[CH:21]=1)[C:4]([O:6][CH2:7][C@H:8]([O:10][C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:12])[CH3:9])=[O:5]

Participants

4

Reactant 3

HCID 6395Methanesulfonic AcidHCID 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 98.5%

Procedure

To an aqueous solution of the hydrochloride salt 3 (65.0 g, 164 mmol, 200 mL) was added aqueous NaHCO3 solution (20.7 g, 246 mmol, 200 mL) and then extracted with EtOAc (2×400 mL). The pooled organic extracts were washed with brine and dried over Na2SO4. After filtration, methanesulfonic acid (12.8 mL, 197 mmol) was slowly added to the filtrate while stirring at room temperature. The resulting white crystals were filtered through a fritted funnel, washed with EtOAc (3×1000 mL) and dried under high vacuum at 50° C. to afford 73.6 g (98.4% yield) of the mesylate salt 1. 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. extractionextracted with EtOAc (2×400 mL)
  2. washThe pooled organic extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. additionwas slowly added to the filtrate
  5. filtrationThe resulting white crystals were filtered through a fritted funnel
  6. washwashed with EtOAc (3×1000 mL)
  7. customdried under high vacuum at 50° C.

Sources & evidence

ORD record
ord-3127c217ac3a4ab2a241fcc5c3ac0cc6
Source dataset
uspto-grants-2009_07
Patent number
US07563821B2

Linked notes

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