Acetic Acid → HCID 70873974, compound

HRID 2208867Notes

Reaction equation

HRID 2208867 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].[CH:21](=O)[CH3:22].C(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]([CH2:21][CH3:22])[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 177Acetaldehyde2×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 70872938Methyl 5-chloro-2-ethyl-3-[(oxan-4-yl)amino]benzoate

Product 1

HCID 70873974HCID 70873974, compoundYield 82.4%

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 acetaldehyde (0.66 ml, 11.8 mmol) followed by acetic acid (0.4 ml, 7.05 mmol). This solution was stirred for 5 minutes before the addition of sodium triacetoxyborohydride (2.49 g, 11.8 mmol) at room temperature. After stirring for 23 hours acetaldehyde (0.66 ml, 11.8 mmol) was added to the dark reaction mixture and this was stirred for 10 minutes before the addition of sodium triacetoxyborohydride (2.49 g, 11.8 mmol). After stirring for 3 hours deionized water (15 ml) was added and the mixture was neutralized with solid NaHCO3. The phases were separated and the aqueous layer was extracted with EtOAc (2×15 ml). 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 317 mg of the title compound as a colorless oil. The product contains ˜25% ether ester. The material was taken through the next step without further purification. LC-MS 55%, 2 m/z=326.0/328.0, 1H NMR (500 MHz, Chloroform-d) δ ppm 7.52 (d, J=2.2 Hz, 1H), 7.23 (d, J=2.2 Hz, 1H), 3.97 (d, J=11.1 Hz, 2H), 3.90 (s, 3H), 3.32 (td, J=11.6, 2.5 Hz, 2H), 3.04 (q, J=7.1 Hz, 4H), 2.93 (ddd, J=15.1, 10.8, 4.3 Hz, 1H), 1.76-1.62 (m, 4H), 1.08 (t, J=7.4 Hz, 3H), 0.88 (t, J=7.1 Hz, 3H).

Workup

  1. additionwas added to the dark reaction mixture
  2. additionwas added
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×15 ml)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. 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-3dab5283dccb4dc8bcdc932c562a522f
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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