(2S,3S)-3-(tert-Butyl-dimethyl-silanyloxy)-2-(4-cyano-naphthalen-1-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester → (2S,3S) 3-Hydroxy-pyrrolidine-2-carboxylic acid (4-cyano-naphthalen-1-yl)-amide

HRID 434076Notes

Reaction equation

HRID 434076 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si](C(C)(C)C)(C)C)[C@H:9]1[C:21](=[O:35])[NH:22][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([C:33]#[N:34])=[CH:25][CH:24]=1)=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[C:33]([C:26]1[C:27]2[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:23]([NH:22][C:21]([C@@H:9]2[C@@H:10]([OH:13])[CH2:11][CH2:12][NH:8]2)=[O:35])=[CH:24][CH:25]=1)#[N:34]

Participants

4

Reactant 1

HCID 69662925(2S,3S)-3-(tert-Butyl-dimethyl-silanyloxy)-2-(4-cyano-naphthalen-1-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59119502(2S,3S) 3-Hydroxy-pyrrolidine-2-carboxylic acid (4-cyano-naphthalen-1-yl)-amideYield 83.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 30C (700 mg, 1.4 mmol) in dry CH2Cl2 (2.8 ml) and TFA (2.8 ml) was stirred at RT for 4 days. The reaction mixture was diluted with CH2Cl2 (35 ml), concentrated to a syrup and stripped with toluene (35 ml) and ether (2×20 ml). The residual syrup was dissolved in water (7.0 ml), basified with 1.0 N NaHCO3 (5.0 ml) to pH 8.0, extracted with CH2Cl2 (2×100 ml) and the combined organic extracts were dried (Na2SO4) and concentrated. Purification by automated flash chromatography (35 g silica gel column, EtOAc/hexane gradient) gave the title compound as an off-white solid (249 mg, 83.4%), m.p. 174-176° C. MS (ES): m/z 282 [M+1]+.

Workup

  1. concentrationconcentrated to a syrup
  2. dissolutionThe residual syrup was dissolved in water (7.0 ml)
  3. extractionextracted with CH2Cl2 (2×100 ml)
  4. dry with materialthe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification by automated flash chromatography (35 g silica gel column, EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-2c95abf104ba4a0d9bf6554f5df7fc40
Source dataset
uspto-grants-2003_12
Patent number
US06670386B2

Reaction notes

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