Iodine → 4-Benzyl-2-(iodomethyl)-2,6,6-trimethylmorpholine

HRID 601555Notes

Reaction equation

HRID 601555 reaction equation
[I:1]I.[CH2:3]([N:10]([CH2:16][C:17]([CH3:19])=[CH2:18])[CH2:11][C:12]([CH3:15])([OH:14])[CH3:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[O-]S([O-])(=S)=O.[Na+].[Na+]>COC(C)(C)C.C([O-])(O)=O.[Na+]>[CH2:3]([N:10]1[CH2:11][C:12]([CH3:13])([CH3:15])[O:14][C:17]([CH2:19][I:1])([CH3:18])[CH2:16]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 574214961-(Benzyl(2-methylallyl)amino)-2-methylpropan-2-ol

Product 1

HCID 574214974-Benzyl-2-(iodomethyl)-2,6,6-trimethylmorpholineYield 93%

Reagents, catalysts & solvents 2

HCID 15413tert-Butyl methyl etherSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Add solid I2 (21.1 g, 83.1 mmol) to a biphasic mixture of 1-[benzyl-(2-methyl-allyl)-amino]-2-methyl-propan-2-ol (17.6 g, 75.4 mmol) in tert-butyl methyl ether (250 mL) and 1 M NaHCO3 (100 mL). Stir for 18 h and then add 1 M Na2S2O3 (100 mL). Dilute the mixture with additional tert-butyl methyl ether (200 mL) and separate the organic solution. Wash the organic solution with a mixture of 1 M Na2S2O3 (100 mL) and 1M NaHCO3 (100 mL). Dry, filter, and concentrate the organic solution. Dry the residue at 60° C. under vacuum to give the title compound (25.2 g, 93%) as a golden oil. 1H NMR (400 MHz, DMSO-d6): δ 7.2-7.4 (5H, m), 3.49 (1H, d), 3.47 (2H, s), 3.41 (1H, s), 2.49 (1H, d), 2.23 (1H, s), 2.20 (1H, s), 2.10 (1H, d), 1.24 (3H, s), 1.22 (3H, s), 1.15 (3H, s).

Workup

  1. customseparate the organic solution
  2. washWash the organic solution
  3. additionwith a mixture of 1 M Na2S2O3 (100 mL) and 1M NaHCO3 (100 mL)
  4. customDry
  5. filtrationfilter
  6. concentrationconcentrate the organic solution
  7. customDry the residue at 60° C. under vacuum

Sources & evidence

ORD record
ord-580b45cd0ea644bf879574c4a0ad14e8
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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