Triethylamine → Dimethylhydroxylamine

HRID 2099355Notes

Reaction equation

HRID 2099355 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:19]([CH2:22]C)CC)C.Cl[C:25](OC(C)(C)C)=[O:26].Cl.[CH3:33][N:34]([CH3:36])[OH:35]>ClCCl>[CH3:33][N:34]([CH3:36])[OH:35].[OH:16][C@H:14]1[CH2:15][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@H:9]([C:10]([N:19]([O:26][CH3:25])[CH3:22])=[O:12])[CH2:13]1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 9920397Tert-butyl Chloroformate

Product 2

HCID 27970DimethylhydroxylamineHCID 15038587HCID 15038587, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1.85 g of (4R)-1-(tert-butoxycarbonyl)-4-hydroxy-L-proline are dissolved in 80 ml of dichloromethane at 0° C. under N2. 3.72 ml of triethylamine and 1.97 ml of tert-butyl chloroformate are added. The reaction medium is stirred at ambient temperature for 1 h. In parallel, a solution of dimethylhydroxylamine is prepared by adding 1.86 ml of triethylamine to a solution of 1.56 g of dimethyl-hydroxylamine hydrochloride in dichloromethane, and then by filtering off the triethylamine hydrochloride. This second solution is added gently, at 0° C., to the first. The reaction medium is stirred at ambient temperature for 16 h. After hydrolysis with a 0.5N aqueous hydrochloric acid solution, extraction is carried out with dichloromethane until the aqueous phase is completely depleted. The organic phase is dried over MgSO4 and concentrated to dryness. 0.9 g of tert-butyl (2S,4R)-4-hydroxy-2-{[methoxy(methyl)amino]-carbonyl}pyrrolidine-1-carboxylate is obtained, which product is subsequently used as it is.

Workup

  1. filtrationby filtering off the triethylamine hydrochloride
  2. additionThis second solution is added gently, at 0° C.
  3. stirringThe reaction medium is stirred at ambient temperature for 16 h
  4. customAfter hydrolysis
  5. extractionwith a 0.5N aqueous hydrochloric acid solution, extraction
  6. dry with materialThe organic phase is dried over MgSO4
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-2ede10b2d9114c268034ef5f37ab298b
Source dataset
uspto-grants-2009_08
Patent number
US07569582B2

Reaction notes

Loading…