Sodium Sulfite → Rotigotine

HRID 2407633Notes

Reaction equation

HRID 2407633 reaction equation
[CH2:1]([NH:4][C@H:5]1[CH2:14][CH2:13][C:12]2[C:11]([OH:15])=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:6]1)[CH2:2][CH3:3].CC1C=CC(S(O[CH2:27][CH2:28][C:29]2[S:30][CH:31]=[CH:32][CH:33]=2)(=O)=O)=CC=1.S([O-])([O-])=O.[Na+].[Na+]>C1(C)C(C)=CC=CC=1>[CH2:1]([N:4]([CH2:27][CH2:28][C:29]1[S:30][CH:31]=[CH:32][CH:33]=1)[C@H:5]1[CH2:14][CH2:13][C:12]2[C:11]([OH:15])=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:6]1)[CH2:2][CH3:3]

Participants

5

Reactant 3

HCID 24437Sodium Sulfite2×HCID 36820342-Thiopheneethanol tosylateHCID 10219902(6S)-6-(Propylamino)-5,6,7,8-tetrahydronaphthalen-1-ol

Product 1

HCID 59227RotigotineYield 53.4%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

2.00 kg (9.74 mol) of (S)-5,6,7,8-tetrahydro-6-propylamino-1-naphthol, 4.12 kg (14.62 mol) of 2-(2-thienyl)ethyl 4-methylbenzenesulfonate (with a sulfonate/starting material mole ratio of 1.5/1), 3.69 kg (29.25 mol) of sodium sulfite (with a sodium sulfite/starting material mole ratio of 3.0/1) and 25 L of xylene were mixed to form a mixture, and the mixture was refluxed. After 48 hours, the reaction was stopped. The mixture was cooled to room temperature, and washed with an appropriate amount of water. Active carbon was added to decolorize the mixture. The mixture was filtered and left standing. An organic phase was reserved and concentrated under vacuum to obtain a residue. The residue was separated by silica gel column chromatography, and eluted with ethyl acetate and hexane (1:19), to obtain 1.64 kg of (S)-5,6,7,8-tetrahydro-6-[propyl[2-(2-thienyl)ethyl]amino]-1-naphthol, which was converted into a hydrochlorate thereof. The yield was 47.8%.

Workup

  1. additionwere mixed to form a mixture
  2. temperaturethe mixture was refluxed
  3. washwashed with an appropriate amount of water
  4. additionActive carbon was added
  5. filtrationThe mixture was filtered
  6. waitleft standing
  7. concentrationconcentrated under vacuum
  8. customto obtain a residue
  9. customThe residue was separated by silica gel column chromatography
  10. washeluted with ethyl acetate and hexane (1:19)

Sources & evidence

ORD record
ord-e5ba036efc6248abbd28ac4522bb2b63
Source dataset
uspto-grants-2014_08
Patent number
US08809590B2

Reaction notes

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