(-)-Pseudoephedrine → Cyclohexanecarboxylate

HRID 928133Notes

Reaction equation

HRID 928133 reaction equation
[CH3:1][NH:2][C@H:3]([CH3:12])[C@@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[OH:5].BrC1SC(C([C@H:22]2[CH2:27][CH2:26][C@H:25]([C:28]([OH:30])=[O:29])[CH2:24][CH2:23]2)(O)C)=NC=1>>[OH:5][C@@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C@@H:3]([NH2+:2][CH3:1])[CH3:12].[CH:25]1([C:28]([O-:30])=[O:29])[CH2:26][CH2:27][CH2:22][CH2:23][CH2:24]1

Participants

4

Reactant 2

HCID 62946(-)-PseudoephedrineHCID 178467399HCID 178467399, compound

Product 2

HCID 168965CyclohexanecarboxylateHCID 6919175(1S,2S)-Pseudoephedrine

Procedure

(1R,2R)-2-(methylamino)-1-phenylpropan-1-ol (0.25 g, 1.50 mmol) was added to a solution of racemic trans-4-[1-(5-bromo-1,3-thiazol-2-yl)-1-hydroxyethyl]cyclohexanecarboxylic acid (500 mg, 1.50 mmol) and the resulting solution was stirred at room temperature overnight, at which point crystallization occurred. The resulting solid was collected by filtration and washed with 1:1 EtOAc:hexane. The resulting mother liquor was concentrated in vacuo and then isopropanol (3.5 mL) and (1S,2S)-2-(methylamino)-1-phenylpropan-1-ol were added. The reaction was stirred overnight, at which point crystallization occurred. Then EtOAc (3 mL) was added and after 20 minutes, the solid was collected via filtration and the filter cake was washed with EtOAc and then dried under a nitrogen bag to afford (1S,2S)-1-hydroxy-N-methyl-1-phenylpropan-2-aminium trans-4-[(1R or 1S)-1-(5-bromo-1,3-thiazol-2-yl)-1-hydroxyethyl]cyclohexanecarboxylate as a white solid. MS ESI calc'd. for C12H17BrNO3S [M+H]+ 334, 336. found 334, 336. 1H NMR (500 MHz, DMSO-d6) δ 7.73 (s, 1H), 7.30-7.27 (m, 4H), 7.25-7.19 (m, 1H), 5.95 (s, 1H), 4.20 (d, J=7.7, 1H), 2.60-2.52 (m, 1H), 2.29 (s, 3H), 2.03-1.92 (m, 1H), 1.92-1.86 (m, 1H), 1.86-1.78 (m, 2H), 1.63-1.52 (m, 1H), 1.48-1.37 (m, 4H), 1.27-1.08 (m, 4H), 1.06-0.89 (m, 1H), 0.68 (d, J=6.4, 3H).

Workup

  1. filtrationThe resulting solid was collected by filtration
  2. washwashed with 1:1 EtOAc
  3. concentrationThe resulting mother liquor was concentrated in vacuo
  4. additionisopropanol (3.5 mL) and (1S,2S)-2-(methylamino)-1-phenylpropan-1-ol were added
  5. stirringThe reaction was stirred overnight, at which point crystallization
  6. additionThen EtOAc (3 mL) was added and after 20 minutes
  7. filtrationthe solid was collected via filtration
  8. washthe filter cake was washed with EtOAc
  9. customdried under a nitrogen bag

Sources & evidence

ORD record
ord-4b2b103b2e024a6b8bf4ad9334a32c14
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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