Acetic Acid → HCID 70873808, compound

HRID 2208852Notes

Reaction equation

HRID 2208852 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].[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]([O:12][CH3:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 177Acetaldehyde3×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride3×HCID 70873748HCID 70873748, compound

Product 1

HCID 70873808HCID 70873808, compoundYield 53.1%

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 (220 mg, 0.73 mmol) in 1,2-dichloroethane (2 ml) at room temperature under nitrogen was added acetaldehyde (82 μl, 1.47 mmol) followed by acetic acid (0.25 ml, 4.4 mmol). This solution was stirred for 5 minutes before the addition of sodium triacetoxyborohydride (0.47 g, 2.2 mmol) at room temperature. After stirring for 16 hours acetaldehyde (82 μl, 1.47 mmol) was added to the reaction mixture and stirred for 5 minutes before the addition of sodium triacetoxyborohydride (0.47 g, 2.2 mmol). After stirring for 24 hours, a further acetaldehyde (82 μl, 1.47 mmol) was added to the reaction mixture and stirred for 5 minutes before the addition of sodium triacetoxyborohydride (0.47 g, 2.2 mmol). The reaction was stirred for 24 h after which deionized water (10 ml) was added and the mixture was neutralized with solid NaHCO3. The phases were separated and the aqueous layer was extracted with EtOAc (2×10 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; 95:5 Heptane:EtOAc to 7:3 Heptane:EtOAc) to give 127 mg (53%) of the title compound as a yellow oil. LC-MS 93%, m/z=328.4/330.0, 1H NMR (500 MHz, Chloroform-d) δ ppm 7.35 (d, J=2.6 Hz, 1H), 7.09 (d, J=2.6 Hz, 1H), 3.98 (dd, J=11.3, 4.2 Hz, 2H), 3.91 (s, 3H), 3.85 (s, 3H), 3.48 (tt, J=11.6, 4.0 Hz, 1H), 3.36 (td, J=11.8, 1.9 Hz, 2H), 3.15 (q, J=7.0 Hz, 2H), 1.78 (qd, J=12.2, 4.6 Hz, 2H), 1.72-1.59 (m, 2H), 0.99 (t, J=7.0 Hz, 3H).

Workup

  1. additionwas added to the reaction mixture
  2. additionwas added
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×10 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; 95:5 Heptane:EtOAc to 7:3 Heptane:EtOAc)

Sources & evidence

ORD record
ord-64ac57d964a54960b4817260cd91b4b6
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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