Boron tribromide → Rotigotine

HRID 1915188Notes

Reaction equation

HRID 1915188 reaction equation
C[O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][C@H:7]([N:13]([CH2:21][CH2:22][CH3:23])[CH2:14][CH2:15][C:16]1[S:17][CH:18]=[CH:19][CH:20]=1)[CH2:8]2.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:23][CH2:22][CH2:21][N:13]([C@@H:7]1[CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:3]([OH:2])[C:4]=2[CH2:5][CH2:6]1)[CH2:14][CH2:15][C:16]1[S:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 58320993(2S)-5-Methoxy-N-propyl-N-[2-(thiophen-2-yl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-amine

Product 1

HCID 59227RotigotineYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a three-necked flask, the (S)-5-methoxy-N-propyl-N-(2′-(thien-2-yl-)ethyl)-tetralin-2-amine (20 g, 61 mmol) prepared above in Example 6 and DCM (300 mL) were added at room temperature, and then cooled to about 0° C. Thereafter, a solution of boron tribromide (73.2 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 react. After the reaction being complete, the mixture was neutralized by the addition of saturated aqueous sodium bicarbonate solution. The organic phase was separated out and concentrated to give crude rotigotine free base. Yield: 100%, Purity: 91%.

Workup

  1. additionwere added at room temperature
  2. additionAfter the addition
  3. temperaturethe temperature was warmed up to room temperature
  4. customto react
  5. customThe organic phase was separated out and
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-54109f064c074adcbd0167577a35a5e9
Source dataset
uspto-grants-2013_12
Patent number
US08614337B2

Reaction notes

Loading…