tert-Butyl bromoacetate → Benzyl 4-(2-oxo-1,3-diazinan-1-yl)piperidine-1-carboxylate

HRID 1278985Notes

Reaction equation

HRID 1278985 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[CH2:22][CH2:21][CH2:20][N:19](CC(O)=O)[C:18]2=[O:27])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].BrCC(OC(C)(C)C)=O>O1CCCC1.ClCCl.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([N:17]2[CH2:22][CH2:21][CH2:20][NH:19][C:18]2=[O:27])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 79177tert-Butyl bromoacetate2×HCID 22137504[3-{1-[(Benzyloxy)carbonyl]piperidin-4-yl}-2-oxotetrahydropyrimidin-1(2H)-yl]acetic acidHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 22137530Benzyl 4-(2-oxo-1,3-diazinan-1-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

1-Benzyloxycarbonyl-4-(3-carboxymethyl-2-oxoperhydropyrimidin-1-yl)piperidine. Potassium tert-butoxide (52 mL, 1 M in tert-butanol) was added to l-benzyloxycarbonyl-4-(2-oxoperhydropyrimidin-1-yl)piperidine (15.0 g), and the solution was stirred for 35 minutes. tert-Butyl bromoacetate (7.65 mL) was then added, and the mixture was stirred overnight. The reaction mixture was diluted with tetrahydrofuran (20 mL) and dichloromethane (10 mL) followed by the addition of tetrabutylammonium iodide (1.74 g), potassium tert-butoxide (52 mL, 1 M in tert-butanol), and tert-butyl bromoacetate (7.65 mL). After being stirred overnight, the reaction mixture was diluted with dichloromethane and washed with water. The separated organic layer was dried, evaporated to an oil, and dissolved in 1 N hydrochloric acid (700 mL), tetrahydrofuran (200 mL), and methanol (200 mL). After being stirred overnight, the reaction mixture was concentrated in vacuo to remove the organic solvents. The resulting aqueous solution was extracted with dichloromethane, acidified with 2 N hydrochloric acid to a pH of 2, and extracted with dichloromethane. The first organic extract was concentrated to give unreacted 1-benzyloxycarbonyl-4-(2-oxoperhydropyrimidin-1-yl)piperidine (7.0 g). The second organic extract was washed with water, dried, and evaporated. The crude product was triturated from ether and filtered to give the title compound as a white solid (8.3 g); MS: m/z=376(M+1); NMR (CDCl3): 7.35 (m,5), 5.12 (s,2), 4.48 (m,1), 4.28 (m,2), 4.02 (s,2), 3.35 (m,2), 3.18 (m,2), 2.87 (m,2), 1.97 (m,2), 1.65 (m,4).

Workup

  1. stirringthe mixture was stirred overnight
  2. stirringAfter being stirred overnight
  3. washwashed with water
  4. customThe separated organic layer was dried
  5. customevaporated to an oil
  6. dissolutiondissolved in 1 N hydrochloric acid (700 mL)
  7. stirringAfter being stirred overnight
  8. concentrationthe reaction mixture was concentrated in vacuo
  9. customto remove the organic solvents
  10. extractionThe resulting aqueous solution was extracted with dichloromethane
  11. extractionextracted with dichloromethane
  12. extractionThe first organic extract
  13. concentrationwas concentrated

Sources & evidence

ORD record
ord-beeb88cae8ed471ea3d3070d044a5d3d
Source dataset
uspto-grants-2002_09
Patent number
US06444809B1

Reaction notes

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