Acetic Acid → HCID 70873837, compound

HRID 2208845Notes

Reaction equation

HRID 2208845 reaction equation
[NH2:1][C:2]1[C:3]([CH3:13])=[C:4]([CH:9]=[C:10]([Cl:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].O=[C:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.O>[Cl:12][C:10]1[CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]([CH3:13])=[C:2]([NH:1][CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH:11]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 68295455Methyl 3-amino-5-chloro-2-methylbenzoate

Product 1

HCID 70873837HCID 70873837, compoundYield 68.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

To a solution of methyl 3-amino-5-chloro-2-methylbenzoate (100 mg, 0.50 mmol) in 1,2-dichloroethane (2.5 ml) at room temperature and under nitrogen was added tert-butyl 4-oxopiperidine-1-carboxylate (200 mg, 1.0 mmol) followed by acetic acid (0.17 ml, 3.0 mmol). This solution was stirred for 5 minutes before the addition of sodium triacetoxyborohydride (0.32 g, 1.5 mmol) at room temperature. The resulting mixture was stirred for 20 hours under nitrogen. Deionized water (5 ml) was added and the mixture was neutralised with solid NaHCO3. The phases were separated and the aqueous layer was extracted with EtOAc (2×5 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 7:3 Heptane:EtOAc) to give 131 mg (68%) of the title compound as a white solid. LC-MS 98%, m/z=405.4/406.9 (M+Na), 1H NMR (500 MHz, Chloroform-d) δ ppm 7.10 (1H, d, J=2.05 Hz), 6.70 (1H, d, J=1.89 Hz), 3.98-4.16 (2H, m), 3.88 (3H, s), 3.58-3.72 (1H, m), 3.37-3.52 (1H, m), 2.97 (2H, br. t, J=11.50, 11.50 Hz), 2.24 (3H, s), 2.06 (2H, br. d, J=10.60 Hz), 1.44-1.51 (9H, m), 1.32-1.44 (2H, m).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous layer was extracted with EtOAc (2×5 ml)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by FCC (10 g silica, Isolute cartridge, gradient of eluents; 99:1 Heptane:EtOAc to 7:3 Heptane:EtOAc)

Sources & evidence

ORD record
ord-e38deb2ebc4d4d51b81906dcbd03da49
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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