Water → N-benzyl[(2R)-6-bromo-3,4-dihydro-2H-chromen-2-yl]methanamine

HRID 896888Notes

Reaction equation

HRID 896888 reaction equation
[BrH:1].[CH2:2]([NH:9][CH2:10][C@H:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[O:12]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.BrBr.O>C(O)=O>[CH2:2]([NH:9][CH2:10][C@H:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([Br:1])[CH:17]=2)[O:12]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 962WaterHCID 24408BromineHCID 69731634N-benzyl[(2R)-3,4-dihydro-2H-chromen-2-yl]methanamine hydrobromide

Product 1

HCID 9923649N-benzyl[(2R)-6-bromo-3,4-dihydro-2H-chromen-2-yl]methanamineYield 84.3%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
16 °C

Procedure

In a 30 L reaction vessel, N-benzyl[(2R)-3,4-dihydro-2H-chromen-2-yl]methanamine hydrobromide (2173 g, 6.5 moles, 1.0 eq.) was suspended in 11.4 L formic acid. The suspension was cooled to 16° C., then bromine (1071 g, 6.7 moles, 1.03 eq.) was added over a 60 minutes, maintaining the reaction temperature between 15 and 16° C. After 70 minutes, a HPLC probe indicated the reaction to be complete. To the reaction mixture was then added 15.6 L water (temperature increased to 21° C.). The light reaction mixture was then stirred for 30 minutes at room temperature, then the product was filtered and washed with 3.9 L water. The 3.14 kg of light gray moist product was then suspended in 9.75 L dichloromethane. To this suspension was added 13 L 1M NaHCO3. Foaming ensued and the suspension became a bi-phasic solution. The aqueous phase was separated (14.5 L; pH=8) and the organic phase was washed with 6.5 L water. The phases were separated and the organic phase evaporated at 45° C. to yield 1820 g of N-benzyl-N-{[(2R)-6-bromo-3,4-dihydro-2H-chromen-2-yl]methyl}amine.

Workup

  1. temperaturemaintaining the reaction temperature between 15 and 16° C
  2. customthe reaction
  3. customThe light reaction mixture
  4. filtrationthe product was filtered
  5. washwashed with 3.9 L water
  6. additionTo this suspension was added 13 L 1M NaHCO3
  7. customThe aqueous phase was separated (14.5 L; pH=8)
  8. washthe organic phase was washed with 6.5 L water
  9. customThe phases were separated
  10. customthe organic phase evaporated at 45° C.

Sources & evidence

ORD record
ord-36d9cfd6a7e549fe8ac2a2950c45d938
Source dataset
uspto-grants-2005_07
Patent number
US06919371B2

Reaction notes

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