Methanesulfonic Acid → Methanesulfonate

HRID 1757456Notes

Reaction equation

HRID 1757456 reaction equation
[NH2:1][C@@H:2]([CH3:6])[C:3]([NH2:5])=[O:4].[BH3-]C#N.[Na+].[F:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=1.[CH3:30][S:31]([OH:34])(=[O:33])=[O:32]>CO>[F:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][NH:1][C@@H:2]([CH3:6])[C:3]([NH2:5])=[O:4])=[CH:24][CH:23]=1.[CH3:30][S:31]([O-:34])(=[O:33])=[O:32]

Participants

7

Reactant 4

HCID 6395Methanesulfonic AcidHCID 444939L-AlaninamideHCID 5003444Sodium cyanoborohydrideHCID 231991044-(3-(2-Fluorophenyl)propyl) oxybenzaldehyde

Product 2

HCID 85257MethanesulfonateHCID 53869583(S)-(+) 2-{4-[3-(2-fluorophenyl)propyl)oxybenzyl}aminopropanamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-(+)-2-aminopropanamide (1.93 g; 0170 mol) in anhydrousmethanol (60 ml), under stirring and nitrogen, 2.0 g of 4 Å molecular sieves were added and then, in a single portion, NaBH3CN (0.78 g; 0.0124 mol); after 10 minutes, 4 g (0.0155 mol) of 4-(3-(2-fluorophenyl)propyl) oxybenzaldehyde were added, in 20 ml of anhydrous methanol. After 3 hours, the reaction was completed, the mixturewas filtered, the filtrates washed with methanol, the residue was directly flash-chromatographed on silica gel (eluant: CH2Cl2 195: CH3OH 5: 30% NH4OH 0.5) to give a white solid (2.7 g; 53%). The free base thus obtained was treated with a stoichiometric amount of methanesulfonic acid to yield (S)-(+) 2-{4-[3-(2-fluorophenyl)propyl)oxybenzyl}aminopropanamide, methanesulfonate; m.p. 172°-177° C.; [α]25 +10.4 (C=1.06, AcOH).

Workup

  1. additionnitrogen, 2.0 g of 4 Å molecular sieves were added
  2. waitAfter 3 hours
  3. filtrationthe mixturewas filtered
  4. washthe filtrates washed with methanol
  5. customthe residue was directly flash-chromatographed on silica gel (eluant: CH2Cl2 195: CH3OH 5: 30% NH4OH 0.5)
  6. customto give a white solid (2.7 g; 53%)
  7. customThe free base thus obtained

Sources & evidence

ORD record
ord-98ee3a78e496482d809cd11e2c1f6a62
Source dataset
uspto-grants-1995_08
Patent number
US05446066

Reaction notes

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