Trifluoroacetic acid → HCID 66601515, compound

HRID 409886Notes

Reaction equation

HRID 409886 reaction equation
[C:1]([NH:9][CH:10]1[CH2:13][N:12]([C:14](OC(C)(C)C)=O)[CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(C(O)=O)(F)(F)F.[C:28]([N:35]1[CH2:38]C(=O)[CH2:36]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C:1]([NH:9][CH:10]1[CH2:11][N:12]([CH:14]2[CH2:38][N:35]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:36]2)[CH2:13]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl ester2×HCID 5049666Sodium triacetoxyborohydride2×HCID 66601302HCID 66601302, compound

Product 1

HCID 66601515HCID 66601515, compoundYield 53.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1c (1.45 g, 5.25 mmol) in CH2Cl2 (20 mL) at room temperature was added CF3CO2H (5 mL). The reaction was stirred at room temperature for 1.5 h. The reaction was concentrated and the resulting residue was dissolved in a mixed solution of 1,2-dichloroethane (10 mL) and acetic acid (0.5 mL). To the resulting solution at room temperature was added 1-Boc-azetidin-3-one 1d (0.99 g, 5.79 mmol), followed by Na(OAc)3BH (1.23 g, 5.80 mmol). The reaction mixture was stirred at room temperature for 20 h. Additional 1-Boc-azetidin-3-one 1d (0.50 g, 2.92 mmol) and Na(OAc)3BH (0.62 g, 2.92 mmol) was added. The reaction was stirred for another 6 h before it was quenched by the addition of aq. NaHCO3. The resulting mixture was extracted with CH2Cl2. The organic solution was dried over Na2SO4 and concentrated. Purification by flash column chromatography (silica gel, 4% MeOH/CH2Cl2) gave compound 1e (0.93 g).

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutionthe resulting residue was dissolved in a mixed solution of 1,2-dichloroethane (10 mL) and acetic acid (0.5 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 20 h
  4. stirringThe reaction was stirred for another 6 h before it
  5. customwas quenched by the addition of aq. NaHCO3
  6. extractionThe resulting mixture was extracted with CH2Cl2
  7. dry with materialThe organic solution was dried over Na2SO4
  8. concentrationconcentrated
  9. customPurification by flash column chromatography (silica gel, 4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-6a3942856a57475db13abec4078220c7
Source dataset
uspto-grants-2014_06
Patent number
US08759533B2

Reaction notes

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