3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → HCID 66823705, compound

HRID 473590Notes

Reaction equation

HRID 473590 reaction equation
C(O[C:6](=O)[NH:7][CH2:8][CH2:9][NH:10][C:11]1[N:16]=[CH:15][CH:14]=[CH:13][N:12]=1)(C)(C)C.[C:18]([N:25]1[CH2:28]C(=O)[CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(O)(C(F)(F)F)=O.C(Cl)Cl.ClCCCl.CC(O)=O>[C:21]([O:20][C:18]([N:25]1[CH2:28][CH:6]([NH:7][CH2:8][CH2:9][NH:10][C:11]2[N:12]=[CH:13][CH:14]=[CH:15][N:16]=2)[CH2:26]1)=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

8

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl ester2×HCID 5049666Sodium triacetoxyborohydride2×HCID 22285237HCID 22285237, compound

Product 1

HCID 66823705HCID 66823705, compoundYield 35.7%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of intermediate 2a (610 mg, 2.56 mmol) in TFA (2 mL) and CH2Cl2 (8 mL) was stirred at room temperature for 2 h. The solution was concentrated. The resulting residue was stirred with N-Boc-azetidin-3-one 1a (526 mg, 3.07 mmol) and Na(OAc)3BH (651, 3.07 mmol) in 1,2-dichloroethane (8 mL) and HOAc (0.8 mL) at room temperature overnight. Additional 1a (175 mg, 1.02 mmol) and Na(OAc)3BH (217 mg, 1.02 mmol) was added. The reaction was stirred for another 5 h before it was quenched with aq. NaHCO3. The resulting mixture was extracted with CH2Cl2. The organic solution was dried over Na2SO4 and concentrated. Purification by column chromatography (silica gel, 6% MeOH/CH2Cl2) gave intermediate 2b as light yellow solid (268 mg).

Workup

  1. concentrationThe solution was concentrated
  2. customwas quenched with aq. NaHCO3
  3. extractionThe resulting mixture was extracted with CH2Cl2
  4. dry with materialThe organic solution was dried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by column chromatography (silica gel, 6% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-aacd1e350c2d4a46b1ed305c1c76e56b
Source dataset
uspto-grants-2014_01
Patent number
US08637498B2

Reaction notes

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