Acetic Acid → HCID 70873976, compound

HRID 2208855Notes

Reaction equation

HRID 2208855 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]([O:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].C=O.[C:23](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.O>[Cl:1][C:2]1[CH:3]=[C:4]([N:14]([CH3:23])[CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]([O:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 70873748HCID 70873748, compound

Product 1

HCID 70873976HCID 70873976, compoundYield 82.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

To a solution of methyl 5-chloro-2-methoxy-3-[(oxan-4-yl)amino]benzoate (500 mg, 1.67 mmol) in 1,2-dichloroethane (16 ml) at room temperature under nitrogen was added paraformaldehyde (300 mg, 10 mmol) followed by acetic acid (0.57 ml, 10 mmol). This mixture was stirred for 5 minutes before the addition of sodium triacetoxyborohydride (2.12 g, 10 mmol). After stirring for 64 hours deionized water (30 ml) was added and the mixture was neutralized with solid NaHCO3 and the phases were separated. The aqueous layer was extracted with EtOAc (3×15 ml) and the combined organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by FCC (10 g silica, Isolute cartridge, gradient of eluents; 9:1 Heptane:EtOAc to 7:3 Heptane:EtOAc) to give 431 mg (82%) of the title compound as a colorless oil. LC-MS 98%, m/z=314.0/316.0, 1H NMR (500 MHz, Chloroform-d) δ ppm 7.30 (d, J=2.5 Hz, 1H), 7.04 (d J=2.5 Hz, 1H), 4.00 (dd, J=11.3, 4.3 Hz, 2H), 3.90 (s, 3H), 3.82 (s, 3H), 3.70 (ddt, J=11.7, 7.7, 3.8 Hz, 1H), 3.39 (t, J=11.1 Hz, 2H), 2.71 (s, 3H), 1.84 (qd, J=12.3, 4.6 Hz, 2H), 1.66-1.55 (m, 2H).

Workup

  1. additionwas added
  2. customthe phases were separated
  3. extractionThe aqueous layer was extracted with EtOAc (3×15 ml)
  4. dry with materialthe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by FCC (10 g silica, Isolute cartridge, gradient of eluents; 9:1 Heptane:EtOAc to 7:3 Heptane:EtOAc)

Sources & evidence

ORD record
ord-3e8fa967d37c4291b001b58b4a302aff
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

Loading…