Acetaldehyde → HCID 178463311, compound

HRID 1050460Notes

Reaction equation

HRID 1050460 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([NH:15][C:16]2[C:17]([CH3:27])=[C:18]([CH:23]=[C:24]([Cl:26])[CH:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:28](=O)[CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.C(O)(=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]([CH2:28][CH3:29])[C:16]2[C:17]([CH3:27])=[C:18]([CH:23]=[C:24]([Cl:26])[CH:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 177AcetaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 178498038HCID 178498038, compound

Product 1

HCID 178463311HCID 178463311, compoundYield 70.8%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent

Procedure

To a solution of methyl 3-(((trans)-4-((tert -butoxycarbonyl)amino)cyclohexyl)amino)-5-chloro-2-methylbenzoate (330 mg, 0.831 mmol) and acetaldehyde (200 μL, 3.56 mmol) in 1,2-dichloroethane (DCE) (5 mL) was added acetic acid (400 μL) and the mixture was stirred at room temperature for 1 h. The mixture was cooled to 0° C. in an ice bath and sodium triacetoxyborohydride (700 mg, 3.30 mmol) was added (very thick suspension that slowly dissolved). The reaction was allowed to warm to room temperature and stirred overnight. LCMS showed the reaction was mostly complete. The reaction was neutralized with sat. NaHCO3, extracted with CH2Cl2, dried (Na2SO4), filtered and concentrated under vacuum. The residue was purified by silica gel chromatography (Analogix, 5 to 20% EtOAc in hexanes) and the pure fractions were combined and evaporated to dryness to give the product methyl 3-(((trans)-4-((tert -butoxycarbonyl)amino)cyclohexyl)(ethyl)amino)-5-chloro-2-methylbenzoate (250 mg, 0.588 mmol, 70.8% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) 6=7.44 (d, J =2.3 Hz, 1 H), 7.38 (d, J=2.3 Hz, 1 H), 6.68 (d, J=7.8 Hz, 1 H), 3.83 (s, 3 H), 3.16 (br. s., 1 H), 3.05 (q, J=6.9 Hz, 2 H), 2.59 (t, J=11.1Hz, 1 H), 2.34 (s, 3 H), 1.82-1.64 (m, 4 H), 1.47-1.38 (m, 2 H), 1.36 (s, 9 H), 1.16-1.04 (m, 2 H), 0.78 (t, J=6.9 Hz, 3 H). MS(ES) [M+H]+ 425.2.

Workup

  1. temperatureThe mixture was cooled to 0° C. in an ice bath
  2. dissolutionslowly dissolved)
  3. temperatureto warm to room temperature
  4. stirringstirred overnight
  5. extractionextracted with CH2Cl2
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by silica gel chromatography (Analogix, 5 to 20% EtOAc in hexanes)
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-d82fa1c1b6b64da79f981fadc7156427
Source dataset
uspto-grants-2016_07
Patent number
US09382234B2

Reaction notes

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