Acetic Acid → HCID 71651084, compound

HRID 1866680Notes

Reaction equation

HRID 1866680 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][NH:11][C:12]2([C:17]([O:19]C)=O)[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:5]=[C:6]([F:8])[CH:7]=1.Cl.[CH2:23]([O:25][C:26](=[O:29])[CH2:27][NH2:28])[CH3:24].CC(O)=O.[BH3-]C#N.[Na+]>CO>[F:8][C:6]1[CH:5]=[C:4]([CH:9]2[N:28]([CH2:27][C:26]([O:25][CH2:23][CH3:24])=[O:29])[C:17](=[O:19])[C:12]3([CH2:13][CH2:14][CH2:15][CH2:16]3)[NH:11][CH2:10]2)[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 2723640Glycine ethyl ester, hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 66955026HCID 66955026, compound

Product 1

HCID 71651084HCID 71651084, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of methyl 1-{[2-(3,5-difluorophenyl)-2-oxoethyl]amino}cyclopentanecarboxylate from Step A (10.0 g, 33.6 mmol), glycine ethyl ester hydrochloride (46.9 g, 336 mmol), and AcOH (5.78 mL, 101 mmol) in MeOH (300 mL) was stirred at ambient temperature for 10 min. NaCNBH3 (2.54 g, 40.4 mmol) was added and the pH of the mixture was checked and adjusted to pH ˜5 as necessary by addition of AcOH. The reaction mixture was heated to 50° C. for 18 h then allowed to cool. The reaction mixture was carefully quenched with saturated aqueous NaHCO3 (250 mL) and then extracted with CH2Cl2 (3×200 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with hexane:EtOAc—100:0 to 0:100, to give the title compound. MS: m/z=353 (M+1).

Workup

  1. temperatureThe reaction mixture was heated to 50° C. for 18 h
  2. temperatureto cool
  3. customThe reaction mixture was carefully quenched with saturated aqueous NaHCO3 (250 mL)
  4. extractionextracted with CH2Cl2 (3×200 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with hexane

Sources & evidence

ORD record
ord-274d7c7f1d294a8c9de2e100a49e8600
Source dataset
uspto-grants-2009_12
Patent number
US07629338B2

Reaction notes

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