Trifluoroacetic acid → 4-Azido-6-iodo-4-methylchroman

HRID 1296095Notes

Reaction equation

HRID 1296095 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][CH2:6][C:5]2([CH3:13])O.[N-:14]=[N+:15]=[N-:16].[Na+].C(O)(C(F)(F)F)=O>C(Cl)(Cl)Cl.O>[N:14]([C:5]1([CH3:13])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([I:1])[CH:3]=2)[O:8][CH2:7][CH2:6]1)=[N+:15]=[N-:16]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 33557Sodium AzideHCID 602068356-Iodo-4-methylchroman-4-ol

Product 1

HCID 602068374-Azido-6-iodo-4-methylchroman

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent2×

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. additiondropwise via addition funnel
  2. additionThe addition
  3. waitcontinued for an additional 2 h at 0° C
  4. stirringstirred over night
  5. extractionextracted with CH2Cl2
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c3f124f4eee3448d8c0b0fbcb23bdfd5
Source dataset
uspto-grants-2007_07
Patent number
US07244725B2

Reaction notes

Loading…