Acetic Acid → HCID 70874014, compound

HRID 2208864Notes

Reaction equation

HRID 2208864 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]([CH2:12][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]([CH2:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712Formaldehyde2×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 70872938Methyl 5-chloro-2-ethyl-3-[(oxan-4-yl)amino]benzoate

Product 1

HCID 70874014HCID 70874014, compoundYield 90.8%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

To a solution of methyl 5-chloro-2-ethyl-3-[(oxan-4-yl)amino]benzoate (350 mg, 1.18 mmol) in 1,2-dichloroethane (10 ml) at room temperature under nitrogen was added paraformaldehyde (212 mg, 7.05 mmol) followed by acetic acid (0.4 ml, 7.05 mmol). This mixture was stirred for 5 minutes before the addition of sodium triacetoxyborohydride (1.49 g, 7.05 mmol). After stirring for 23 hours, further paraformaldehyde (212 mg, 7.05 mmol) was added to the reaction mixture and this was stirred for 10 minutes before the addition of sodium triacetoxyborohydride (1.49 g, 7.05 mmol). After stirring for 3 hours, deionized water (15 ml) was added and the mixture was neutralized with solid NaHCO3 and the phases were separated. The aqueous layer was extracted with EtOAc (2×15 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; 99:1 Heptane:EtOAc to 85:15 Heptane:EtOAc) to give 334 mg of the title compound as a colorless oil. The product contains ˜22% ethyl ester. The material was taken through the next step without further purification. LC-MS 56%, m/z=312.0/314.0, 1H NMR (500 MHz, Chloroform-d) δ ppm 7.52 (d, J=2.2 Hz, 1H), 7.24 (d, J=2.2 Hz, 1H), 4.01-3.93 (m, 2H), 3.89 (s, 3H), 3.34 (td, J=11.7, 2.3 Hz, 2H), 3.06-2.96 (m, 2H), 2.94-2.85 (m, 1H), 2.61 (s, 3H), 1.76-1.59 (m, 4H), 1.10 (t, J=7.4 Hz, 3H).

Workup

  1. stirringAfter stirring for 3 hours
  2. customthe phases were separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×15 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; 99:1 Heptane:EtOAc to 85:15 Heptane:EtOAc)

Sources & evidence

ORD record
ord-7170d11e33e14c3f926e4d96d16a1da9
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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