Tetrahydrofuran → N-(tert-Butoxycarbonyl)-D-prolinol

HRID 359466

Reaction equation

HRID 359466 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@@H:12]([C:13](O)=[O:14])[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].O1CCCC1>CCOCC>[OH:14][CH2:13][C@H:12]1[CH2:11][CH2:10][CH2:9][N:8]1[C:6]([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:7]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 688279N-(tert-Butoxycarbonyl)-D-prolinol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

In accordance with Scheme I, N-α-t-BOC-D-proline 2a is reacted in an ether solvent such as tetrahydrofuran at a temperature ranging from -2° C. to the reflux temperature of the solvent with 10M borane-methyl sulfide complex to produce (R)-2-(hydroxymethyl)-1pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester 3a. Compound 3a in a chlorinated hydrocarbon solvent such as methylene chloride is treated with an oxidizing agent such as pyridinium chlorochromate, 4Å molecular sieves and glacial acetic acid to give (R)-2-formyl-1-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester 4a. Compound 4a in methylene chloride is treated with a methylene chloride solution of triphenylphosphine and carbon tetrabromide to produce (R)-2-(2,2-dibromoethenyl)-1pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester 5a. The dibromo compound 5a in an ether solvent such as tetrahydrofuran is reacted at -78° C. with an alkyl lithium reagent such as sec-butyllithium to give (R)-2-ethynyl-1-pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester 6a.

Workup

  1. customranging from -2° C. to the reflux temperature of the solvent with 10M borane-methyl sulfide complex

Sources & evidence

ORD record
ord-664d777b58a34bb594a391cf354d1f08
Source dataset
uspto-grants-1991_03
Patent number
US05001142

Linked notes

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