Sodium Iodide → 1-Tert-butoxycarbonylamino-2-(2-cyano-ethyl)-cyclopropanecarboxylic acid methyl ester

HRID 2405816Notes

Reaction equation

HRID 2405816 reaction equation
[CH3:1][O:2][C:3]([C:5]1([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:7][CH:6]1[CH2:8][CH2:9]OS(C)(=O)=O)=[O:4].[C-:23]#[N:24].[Na+].[Na+].[I-]>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:7][CH:6]1[CH2:8][CH2:9][C:23]#[N:24])=[O:4]

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 8929Sodium CyanideHCID 574451671-Tert-butoxycarbonylamino-2-(2-methanesulfonyloxyethyl)cyclopropanecarboxylic acid methyl ester

Product 1

HCID 686185231-Tert-butoxycarbonylamino-2-(2-cyano-ethyl)-cyclopropanecarboxylic acid methyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To 1-tert-butoxycarbonylamino-2-(2-methanesulfonyloxy-ethyl)-cyclopropanecarboxylic acid methyl ester (400 mg, 1.19 mmol) from example 109 in DMF (6 mL) was added NaCN (350 mg, 7.14 mmol) and NaI (178 mg, 1.19 mmol). The reaction mixture was heated at 80° C. for 2 h then diluted with EtOAc and washed with water and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography on silica (20→50% EtOAc/Hexanes) to afford 1-tert-butoxycarbonylamino-2-(2-cyano-ethyl)-cyclopropanecarboxylic acid methyl ester (297 mg, 93%). 1H NMR (300 MHz, CDCl3): δ 5.13 (br s, 1H), 2.44 (m, 2H), 2.05 (m, 2H), 1.70-1.53 (m, 1H), 1.53-1.37 (m, 4H) 1.45 (s, 9H). LCMS found 290.9 [M+Na]+. To this intermediate (297 mg, 1.10 mmol) in CH2Cl2 (2 mL) was added 4N HCl in dioxanes (2 mL). Ater stirring at room temperature for 2 h the reaction was concentrated to afford 225 mg (100%) of the HCl salt of 1-amino-2-(2-cyano-ethyl)-cyclopropanecarboxylic acid methyl ester, which was used in the next step without further purification.

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography on silica (20→50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-05135eee2efa459c9d47c1db831f9239
Source dataset
uspto-grants-2014_08
Patent number
US08809267B2

Reaction notes

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