Benzyl Bromide → HCID 69505881, compound

HRID 362628Notes

Reaction equation

HRID 362628 reaction equation
[CH:1]1[C:17]2[CH2:16][C@H:15]3[N:18]([CH2:20][CH2:21][C@@:7]45[C@H:14]3[CH:13]=[CH:12][C@H:10]([OH:11])[C@@H:8]4[O:9][C:5]([C:6]=25)=[C:3]([OH:4])[CH:2]=1)[CH3:19].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[OH-].[Na+]>C1COCC1.C(Cl)Cl>[CH2:22]([C:3]1([OH:4])[C:5]2[O:9][C@@H:8]3[C@@:7]45[CH2:21][CH2:20][N:18]([CH3:19])[C@@H:15]([C@@H:14]4[CH:13]=[CH:12][C@@H:10]3[OH:11])[CH2:16][C:17]([C:6]5=2)=[CH:1][CH2:2]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 14798Sodium HydroxideHCID 5288826Morphine

Product 1

HCID 69505881HCID 69505881, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of morphine (10.0 g, 35.1 mmol) in THF (200 ml), was added benzyl bromide (5.5 ml, 98%, 45.3 mmol) and sodium hydroxide (1.48 g, 37.0 mmol) at 0° C. The reaction mixture was stirred overnight. The reaction temperature rose gradually to rt. during the process. THF in the reaction mixture was removed on a rotary evaporator. The residue was dissolved in CH2Cl2 (150 ml) and water (50 ml). The organic layer was separated. The aqueous layer was extracted with CH2Cl2 (3×50 ml). The combined organic layer was dried over anhydrous sodium sulfate, evaporated in vacuo to obtain a crude product (13 g), which was dissolved in CH2Cl2 and loaded onto a silica gel column (3×30 cm). The column was first eluted with 3% methanol in CH2Cl2, followed by 5% methanol in CH2Cl2. Pure fractions were combined to obtain 3-benzylmorphine (7.9 g, 60% yield). IR (KBr)(ν, cm-1): 3540 (m, sharp, --OH), 3020 (m, sharp), 2900 (s, sharp), 1600 (m, sharp); NMR (δH)(CDCl3): 7.50-7.20 (5, m, --C6H5), 6.70 (1, d, J, 8.1, 2-H), 6.51 (1, dd, J, 8.1 & 0.9, 1-H), 5.65 (1, dm, J, 9.9, 7-H), 5.26 (1, dt, J, 9.9 & 2.5, 8-H), 5.12 (2, AB, OCH2Ph), 4.85 (1, dd, J, 6.6 & 1.2, 5-H), 4.22-4.05 (1, m, 6-H), 3.32 (1, dd, J, 6.2 & 3.3, 9-H), 3.02 (1, d, J, 18.6, 10-Hβ), 2.75-2.65 (1, m, 14-H), 2.75-2.65 (1, b, --OH), 2.58 (1, dm, J, 12.0, 16-He), 2.5-2.3 (1, m, 16Ha) 2.42 (3, s, N--CH3), 2.27 (1, dd, J, 18.6 & 6.6, 10-Hα), 2.05 (1, td, J, 12.1 & 5.3, 15-Ha), 1.85 (1, dm, J, 12.5, 15-He).

Workup

  1. customrose gradually to rt
  2. customTHF in the reaction mixture was removed on a rotary evaporator
  3. dissolutionThe residue was dissolved in CH2Cl2 (150 ml)
  4. customThe organic layer was separated
  5. extractionThe aqueous layer was extracted with CH2Cl2 (3×50 ml)
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  7. customevaporated in vacuo
  8. customto obtain a crude product (13 g), which
  9. washThe column was first eluted with 3% methanol in CH2Cl2

Sources & evidence

ORD record
ord-75dea7955f6241948d9069e47db3691e
Source dataset
uspto-grants-1999_02
Patent number
US05869669

Reaction notes

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