Water → 6-Iodo-4-methylchroman-4-amine

HRID 1296096Notes

Reaction equation

HRID 1296096 reaction equation
[N-]=[N+]=[N-].[N:4]([C:7]1([CH3:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([I:17])[CH:15]=2)[O:10][CH2:9][CH2:8]1)=[N+]=[N-].CP(C)C.O>C1COCC1>[I:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[O:10][CH2:9][CH2:8][C:7]2([CH3:18])[NH2:4]

Participants

6

Reactant 4

HCID 962WaterHCID 33558AzideHCID 68983TrimethylphosphineHCID 602068374-Azido-6-iodo-4-methylchroman

Product 1

HCID 602068366-Iodo-4-methylchroman-4-amineYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 6-iodo-4-methylchroman-4-ol (1.0 g, 3.4 mmol) and NaN3 (0.7 g, 10.3 mmol) in CHCl3 (15 ml), at 0° C., was added TFA (1.3 ml, 17.2 mmol) as a solution in 10 ml of CHCl3 dropwise via addition funnel. The addition was carried out over 2 h and stirring continued for an additional 2 h at 0° C. The mixture was warmed to r.t. and stirred over night. The mixture was diluted with 30 ml of water and extracted with CH2Cl2. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield 4-azido-6-iodo-4-methylchroman as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J=2.07 Hz, 1H), 7.50 (dd, J=8.71, 2.07 Hz, 1H), 6.66 (d, J=8.71 Hz, 1H), 4.27 (m, 2H), 2.06 (m, 2H), 1.68 (s, 3H). MS (ESI+) for C10H10IN3O m/z 273.0 (M+H)+ loss of azide. The crude azide was dissolved in THF (15 ml) followed by the addition of trimethylphosphine (4 ml, 1.0 M in THF) at r.t. After 15 min. 3 ml of water was added and stirring continued at r.t. for 2 h until complete as indicated by LC/MS. The solvent was removed in vacuo and the residue diluted with water (75 ml) and extracted with CH2Cl2 (3×50 ml). The organic layer was dried over Na2SO4 and concentrated in vacou to yield 6-iodo-4-methylchroman-4-amine (0.900 g, 91%) as a yellow oil. This material was used in the next step without purification. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J=2.07 Hz, 1H), 7.40 (dd, J=8.60, 2.18 Hz, 1H), 6.59 (d, J=8.50 Hz, 1H), 4.25 (m, 2H), 2.01 (m, 2H), 1.53 (s, 3H). MS (ESI+) for C10H12INO m/z 273.2 (M+H)+ loss of NH3.

Workup

  1. waitcontinued at r.t. for 2 h
  2. customThe solvent was removed in vacuo
  3. additionthe residue diluted with water (75 ml)
  4. extractionextracted with CH2Cl2 (3×50 ml)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-541d64d99b09458ba9a0568d2e4d3f94
Source dataset
uspto-grants-2007_07
Patent number
US07244725B2

Reaction notes

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