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

HRID 47682Notes

Reaction equation

HRID 47682 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>C(O)(=O)C>[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

4

Reactant 2

HCID 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 95.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
16 °C

Procedure

In a 500-mL round bottom flask, N-benzyl[(2R)-3,4-dihydro-2H-chromen-2-yl]methanamine hydrobromide (33.4 g, 0.1 mole, 1.0 eq.) was suspended in 240 mL of acetic acid. The suspension was cooled to 16° C., then bromine (16 g, 0.1 mole, 1.0 eq.) was added over 20 minutes, maintaining the reaction temperature between 15-16° C. After 60 minutes, an HPLC analysis indicated the reaction was complete. The reaction mixture was then stirred for 30 minutes at room temperature, and the product was collected by filtration. The light gray moist product was suspended in dichloromethane (200 mL) and to this suspension was added 0.5M NaHCO3 (350 mL). 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 50 mL water. The phases were separated and the organic phase concentrated in vacuo at 45° C. to yield 31.6 g of N-benzyl-N-{[(2R)-6-bromo-3,4-dihydro-2H-chromen-2-yl]methyl}amine. NMR (DMSO-d6) δ1.56 (m, 1H), 2.02 (m, 1H), 2.25 (bs, 1H), 2.73 (m, 4H), 3.75 (s, 2H), 4.05 (m, 1H), 6.70 (d, J=8.8 Hz, 1H), 7.25-7.40 (m, 7H); MS (El): m/z 232 (MH+), 234 (M+2).

Workup

  1. temperaturemaintaining the reaction temperature between 15-16° C
  2. filtrationthe product was collected by filtration
  3. additionwas added 0.5M NaHCO3 (350 mL)
  4. customThe aqueous phase was separated (14.5 L; pH=8)
  5. washthe organic phase was washed with 50 mL water
  6. customThe phases were separated
  7. concentrationthe organic phase concentrated in vacuo at 45° C.

Sources & evidence

ORD record
ord-785cab3528fb403c878501137f27b603
Source dataset
uspto-grants-2004_03
Patent number
US06699860B2

Reaction notes

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