Acetic Acid → HCID 58697218, compound

HRID 2212029Notes

Reaction equation

HRID 2212029 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]([O:19][C:20]([N:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[CH:27]=O)=[O:21])([CH3:18])([CH3:17])[CH3:16].[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1.C(O)(=O)C>ClCCl>[C:15]([O:19][C:20]([N:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[CH2:27][N:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 2734674tert-butyl (2S)-2-formylpyrrolidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 58697218HCID 58697218, compoundYield 64.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Sodium triacetoxyborohydride (35.7 g, 0.168 mol) was added to a mixture of crude (S)-2-formylpyrrolidine-1-carboxylic acid tert-butyl ester (11.2 g, 0.056 mol), pyrrolidine (5.16 ml, 0.062 mol) and mol sieves (10 g) in dichloromethane (100 ml). Acetic acid (6.42 g, 0.112 mol) was added. The reaction mixture was stirred for 16 hours at room temperature. The precipitation was removed by filtration. The filtrate was diluted with a 1 N aqueous solution of sodium hydroxide (100 ml) and tert-butyl methyl ether (100 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (3×80 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (90 g), using ethyl acetate/heptane/triethylamine (1:1, 5%) as eluent, to give 9.23 g of (S)-2-((pyrrolidin-1-yl)methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. customThe precipitation
  2. customwas removed by filtration
  3. additionThe filtrate was diluted with a 1 N aqueous solution of sodium hydroxide (100 ml) and tert-butyl methyl ether (100 ml)
  4. customThe phases were separated
  5. extractionThe aqueous phase was extracted with tert-butyl methyl ether (3×80 ml)
  6. dry with materialThe combined organic layers were dried over magnesium sulphate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatography on silica (90 g)

Sources & evidence

ORD record
ord-9aed42fa76ff4a97aef5237a0ef1d636
Source dataset
uspto-grants-2006_09
Patent number
US07101898B2

Reaction notes

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