Acetic Acid → 1,1-Dimethylethyl 2-[[[[4-(methoxycarbonyl)phenyl]methyl]amino]methyl]-1-pyrrolidinecarboxylate

HRID 16493

Reaction equation

HRID 16493 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[CH:15]([C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=1)=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[CH3:24][O:23][C:21]([C:20]1[CH:25]=[CH:26][C:17]([CH2:15][NH:1][CH2:2][CH:3]2[CH2:7][CH2:6][CH2:5][N:4]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[CH:18][CH:19]=1)=[O:22]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 15294Methyl 4-FormylbenzoateHCID 516892Sodium BicarbonateHCID 2756484(+-)-2-(Aminomethyl)-1-N-Boc-pyrrolidineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 684903891,1-Dimethylethyl 2-[[[[4-(methoxycarbonyl)phenyl]methyl]amino]methyl]-1-pyrrolidinecarboxylateYield 45.9%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 1,1-dimethylethyl 2-(aminomethyl)-1-pyrrolidinecarboxylate (1000 mg, 5 mmol) and methyl 4-formylbenzoate (820 mg, 5 mmol) in dichloroethane was stirred as acetic acid (450 mg, 7.5 mmol) and sodium triacetoxyborohydride (1271 mg, 6 mmol) were added sequentially at ambient temperature. After stirring at ambient temperature for 17 hours, treated with a saturated aqueous solution of sodium bicarbonate and extracted with EtOAc. The combined organic extracts were dried and concentrated. Purification by flash chromatography afforded 1,1-dimethylethyl 2-[[[[4-(methoxycarbonyl)phenyl]methyl]amino]methyl]-1-pyrrolidinecarboxylate (800 mg), 1H NMR (CDCl3) 7.98 (d, 2H), 3.37 (d, 2H), 3.91 (s, 3H), 3.82 (s, 2H), 3.36 (m, 2H), 2.72 (m, 1H), 1.82 (m, 3H), 1.44 (m, 2H) ppm.

Workup

  1. additionwere added sequentially at ambient temperature
  2. extractionextracted with EtOAc
  3. customThe combined organic extracts were dried
  4. concentrationconcentrated
  5. customPurification by flash chromatography

Sources & evidence

ORD record
ord-3b4210f7d06a4dc6972f9660db0df2d9
Source dataset
uspto-grants-2010_06
Patent number
US07737145B2

Linked notes

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