Acetic Acid → (+/-) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylate

HRID 1430864Notes

Reaction equation

HRID 1430864 reaction equation
[OH:1][CH2:2][CH:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.[O:16]1[CH2:19][C:18](=O)[CH2:17]1.CC(O)=O.C([BH3-])#N.[Na+]>C(Cl)Cl.CO>[OH:1][CH2:2][CH:3]1[N:8]([CH:18]2[CH2:19][O:16][CH2:17]2)[CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 223865084-N-Boc-2-hydroxymethylpiperazine

Product 1

HCID 86708556(+/-) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylateYield 62.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(+/−) Tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (3.07 g, 14.19 mmol), oxetan-3-one (1.820 mL, 28.4 mmol), AcOH (1.625 mL, 28.4 mmol), and 4 Å molecular sieves were taken up in DCM (16 mL) and MeOH (16.00 mL), and the reaction was stirred at rt overnight. Sodium cyanoborohydride (4.46 g, 71.0 mmol) was added and the reaction was stirred at rt for 2 h. The reaction mixture was filtered through celite, rinsing with MeOH. The solvent was removed in vacuo and the material was quenched with 2M K3PO4 solution, then extracted 2× with EtOAc. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-8% MeOH/DCM). (+/−) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylate (2.40 g) was obtained as a colorless oil.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. washrinsing with MeOH
  3. customThe solvent was removed in vacuo
  4. customthe material was quenched with 2M K3PO4 solution
  5. extractionextracted 2× with EtOAc
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe material was purified by flash column chromatography (0-8% MeOH/DCM)

Sources & evidence

ORD record
ord-7844771d58ec4f86a3f67a4c24cb5695
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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