Trifluoroacetic acid → Methyl 5-(azetidin-3-yl)-2-methyl-3-[methyl(oxan-4-yl)amino]benzoate

HRID 2208818Notes

Reaction equation

HRID 2208818 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:20]2[CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]2)[CH:8]=[C:9]([N:12]([CH3:19])[CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:10]=1[CH3:11])=[O:4].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:22]1[CH2:21][CH:20]([C:7]2[CH:8]=[C:9]([N:12]([CH3:19])[CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[C:10]([CH3:11])=[C:5]([CH:6]=2)[C:3]([O:2][CH3:1])=[O:4])[CH2:23]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86719565Tert-butyl 3-[3-(methoxycarbonyl)-4-methyl-5-[methyl(oxan-4-yl)amino]phenyl]azetidine-1-carboxylate

Product 1

HCID 70873962Methyl 5-(azetidin-3-yl)-2-methyl-3-[methyl(oxan-4-yl)amino]benzoateYield 121%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 3-[3-(methoxycarbonyl)-4-methyl-5-[methyl(oxan-4-yl)amino]phenyl]azetidine-1-carboxylate (400 mg, 0.96 mmol) in DCM (4 ml) was added TFA (1 ml) and the solution was stirred at room temperature for 45 min after which the solvent was evaporated to dryness and saturated aqueous NaHCO3 was added until pH7-8. The aqueous phase was extracted with DCM (3×30 ml), washed with brine (30 ml), dried with MgSO4, filtered and evaporated to afford the title compound as an orange oil (370 mg, 95%). LC-MS 96%, m/z=319.1, 1H NMR (500 MHz, Chloroform-d) δ 7.49 (d, J=1.4 Hz, 1H), 7.20 (d, J=1.3 Hz, 1H), 4.32-4.10 (m, 5H), 3.98 (d, J=11.0 Hz, 2H), 3.90 (d, J=8.4 Hz, 3H), 3.34 (t, J=10.8 Hz, 2H), 2.99 (ddd, J=14.7, 10.9, 3.8 Hz, 1H), 2.65 (d, J=8.3 Hz, 3H), 2.51-2.41 (m, 3H), 1.73 (ddd, J=15.7, 12.1, 4.3 Hz, 2H), 1.64 (d, J=11.2 Hz, 2H).

Workup

  1. customwas evaporated to dryness and saturated aqueous NaHCO3
  2. additionwas added until pH7-8
  3. extractionThe aqueous phase was extracted with DCM (3×30 ml)
  4. washwashed with brine (30 ml)
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-141f48fc98874571ac944198f7462225
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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