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

HRID 2427422Notes

Reaction equation

HRID 2427422 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-a80701bb52034857b554b889943d4963
Source dataset
uspto-grants-2011_06
Patent number
US07968597B2

Reaction notes

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