1,2-Dichloroethane → tert-butyl (2R,5R)-4-benzyl-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate

HRID 1475405Notes

Reaction equation

HRID 1475405 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]([CH3:14])[CH2:12][N:11]([C:15](OCC2C=CC=CC=2)=O)[C@@H:10]([CH2:25][OH:26])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].ClCCCl>CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@H:10]([CH2:25][OH:26])[N:11]([CH2:15][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:12][C@H:13]1[CH3:14])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 240BenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 867239281-Benzyl 4-(tert-butyl) (2R,5R)-2-(hydroxymethyl)-5-methylpiperazine-1,4-dicarboxylate

Product 1

HCID 70980613tert-butyl (2R,5R)-4-benzyl-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylateYield 94.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of (2R,5R)-2-hydroxymethyl-5-methyl-piperazine-1,4-dicarboxylic acid 1-benzyl ester 4-tert-butyl ester (3.48 g, 15.1 mmol), benzaldehyde (1.76 g, 16.6 mmol), sodium triacetoxyborohydride (3.84 g, 18.1 mmol) and 1,2-dichloroethane (30 mL) was stirred at 20° C. for 18 h, then partitioned between saturated aqueous NaHCO3 (150 mL) and DCM (3×50 mL). Combined organic extracts were dried (Na2SO4) then evaporated in vacuo to give an oil. Chromatography (SiO2, 0-30% EtOAc in petrol) gave the title compound (4.588 g, 74%) as a colourless solid. MS: [M+H]+=321.

Workup

  1. custompartitioned between saturated aqueous NaHCO3 (150 mL) and DCM (3×50 mL)
  2. dry with materialCombined organic extracts were dried (Na2SO4)
  3. customthen evaporated in vacuo
  4. customto give an oil

Sources & evidence

ORD record
ord-628beec05e2744709aa1cadf58ac8438
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

Loading…