Acetic Acid → HCID 66774296, compound

HRID 1644801Notes

Reaction equation

HRID 1644801 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1([CH:14]=O)[CH3:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:16][C:17]1[CH:24]=[CH:23][CH:22]=[CH:21][C:18]=1[CH2:19][NH2:20].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1([CH2:14][NH:20][CH2:19][C:18]1[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=1[Cl:16])[CH3:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 666482-ChlorobenzylamineHCID 5049666Sodium triacetoxyborohydrideHCID 22456683Tert-butyl 2-formyl-2-methylpyrrolidine-1-carboxylate

Product 1

HCID 66774296HCID 66774296, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (rac)-2-formyl-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.7 g, 1 eq) and 2-chloro-benzylamine (1.2 eq) in DCE (20 mL) was added acetic acid (0.8 eq) and allowed to stir for 20 minutes followed by the addition of sodium triacetoxyborohydride (2 eq). The reaction mixture was stirred for 12 h. After completion of reaction on TLC, the reaction was quenched with water and extracted with DCM (3×50 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated using rotary evaporator to give sticky crude product, which was then purified with column chromatography (2-5% Methanol:DCM, Mesh Size-100-200 silica, Diameter of column—3.0 cm, Height of silica—approx. 4 inch) to afford the desired (rac)-2-[(2-chloro-benzylamino)-methyl]-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester as a sticky solid (40-70%).

Workup

  1. stirringThe reaction mixture was stirred for 12 h
  2. customAfter completion of reaction on TLC
  3. customthe reaction was quenched with water
  4. extractionextracted with DCM (3×50 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customevaporator
  8. customto give sticky crude product, which
  9. customwas then purified with column chromatography (2-5% Methanol:DCM, Mesh Size-100-200 silica, Diameter of column—3.0 cm, Height of silica—approx. 4 inch)

Sources & evidence

ORD record
ord-c014eff3b9c4414f9e703ee1cdf81f31
Source dataset
uspto-grants-2012_02
Patent number
US08124636B2

Reaction notes

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