2,2-Dimethyl-1,3-dioxane-4,6-dione → (R)-[1-(2,2-Dimethyl-4,6-dioxo-[1,3]dioxane-5-carbonyl)-2-methyl-propyl]-carbamic acid tert-butyl ester

HRID 491903Notes

Reaction equation

HRID 491903 reaction equation
[C:1]([NH:8][C@@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:16][C:17]1([CH3:25])[O:24][C:22](=[O:23])[CH2:21][C:19](=[O:20])[O:18]1>ClCCl>[C:4]([O:3][C:1](=[O:2])[NH:8][C@@H:9]([C:13]([CH:21]1[C:22](=[O:23])[O:24][C:17]([CH3:25])([CH3:16])[O:18][C:19]1=[O:20])=[O:15])[CH:10]([CH3:11])[CH3:12])([CH3:5])([CH3:6])[CH3:7]

Participants

4

Reactant 2

HCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 58856323(R)-[1-(2,2-Dimethyl-4,6-dioxo-[1,3]dioxane-5-carbonyl)-2-methyl-propyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
3 °C

Procedure

A 5 L four-necked flask (equipped with mechanical stirrer, nitrogen inlet, thermocouple, and glass stopper) was charged with Boc-D-Valine (143.6 g, 0.661 mol) and dichloromethane (2.8 L). The reaction was chilled to ˜3° C. in an ice bath, and then 4-N,N-dimethylaminopyridine (124.6 g, 1.02 mol) and Meldrum's acid (104.8 g, 0.727 mol) were added to the reaction. To the reaction mixture was then added 1-[3-(dimethylaminopropyl)]-3-ethylcarbodiimide hydrochloride (EDCl, 139.4 g, 0.727 mol) over a five-minute period, and then the reaction mixture was allowed to warm to room temperature over 18 h (overnight). The reaction mixture washed with 5% (w/w) aqueous potassium bisulfate (4×600 mL), dried (MgSO4), and the solution was used directly in the next step without concentration or purification. A small portion was concentrated and displayed the following analytical data.

Workup

  1. customA 5 L four-necked flask (equipped with mechanical stirrer, nitrogen inlet
  2. temperatureto warm to room temperature over 18 h (overnight)
  3. washThe reaction mixture washed with 5% (w/w) aqueous potassium bisulfate (4×600 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationthe solution was used directly in the next step without concentration or purification
  6. concentrationA small portion was concentrated

Sources & evidence

ORD record
ord-d74dd21795f34a61bd3ea70a079ed615
Source dataset
uspto-grants-2009_05
Patent number
US07531545B2

Reaction notes

Loading…