Boron tribromide → Rotigotine hydrochloride

HRID 1915190Notes

Reaction equation

HRID 1915190 reaction equation
[ClH:1].C[O:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][C@H:8]([N:14]([CH2:22][CH2:23][CH3:24])[CH2:15][CH2:16][C:17]1[S:18][CH:19]=[CH:20][CH:21]=1)[CH2:9]2.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:24][CH2:23][CH2:22][N:14]([C@@H:8]1[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[C:4]([OH:3])[C:5]=2[CH2:6][CH2:7]1)[CH2:15][CH2:16][C:17]1[S:18][CH:19]=[CH:20][CH:21]=1.[ClH:1]

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 68654246N-Propyl-N-[(2S)-1,2,3,4-tetrahydro-5-methoxy-2-naphthalenyl]-2-thiopheneethanamine hydrochloride

Product 1

HCID 180335Rotigotine hydrochlorideYield 79.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a 10 L three-necked flask, the (S)-5-methoxy-N-propyl-N-(2′-(thien-2-yl-)ethyl)-tetralin-2-amine hydrochloride (295 g, 0.9 mol) prepared above in Example 7 and 5.5 kg DCM were added at room temperature, and then cooled to a temperature of 0° C.-5° C. Thereafter, a 1 M solution of boron tribromide (1.08 mmol) in dichloromethane (concentration: 1 g/3.8 mL) was added dropwise to the reaction liquid. After the addition, the temperature was warmed up to room temperature to perform the reaction. After the reaction being complete, the mixture was neutralized by the addition of saturated aqueous sodium bicarbonate solution, and left alone and partitioned. The organic phase was adjusted to be acidic by the addition of an aqueous hydrochloride solution or an organic solution of hydrogen chloride or by the introduction of hydrochloride gas. The mixture was filtered, and the filter cake was washed with DCM and dried overnight to give crude rotigotine hydrochloride. Yield: 79.5%, Purity: 98.2%.

Workup

  1. additionwere added at room temperature
  2. temperaturecooled to a temperature of 0° C.-5° C
  3. additionAfter the addition
  4. customthe reaction
  5. waitleft alone
  6. custompartitioned
  7. additionto be acidic by the addition of an aqueous hydrochloride solution
  8. filtrationThe mixture was filtered
  9. washthe filter cake was washed with DCM
  10. customdried overnight

Sources & evidence

ORD record
ord-5484f429872e499a8f54649559db31e5
Source dataset
uspto-grants-2013_12
Patent number
US08614337B2

Reaction notes

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