Methanol → tert-Butyl 3-(hydroxymethyl)azetidine-1-carboxylate

HRID 1627562Notes

Reaction equation

HRID 1627562 reaction equation
[N:1]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4][CH:3]([C:5](OC)=[O:6])[CH2:2]1.CO.[Li+].[BH4-].O.O.O.O.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C1COCC1.CCOC(C)=O>[OH:6][CH2:5][CH:3]1[CH2:4][N:1]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:2]1

Participants

7

Reactant 4

HCID 887MethanolHCID 2724148Sodium potassium tartrate tetrahydrateHCID 4148881Lithium borohydrideHCID 446076271-tert-Butyl 3-methyl azetidine-1,3-dicarboxylate

Product 1

HCID 10583745tert-Butyl 3-(hydroxymethyl)azetidine-1-carboxylateYield 73.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

1-tert-butyl 3-methyl azetidine-1,3-dicarboxylate (1055 mg, 4.90 mmol) was dissolved in THF (17 mL) and then cooled to 0° C. MeOH (0.397 mL, 9.80 mmol) and LiBH4 (14.7 mmol) were added sequentially. The reaction was warmed to room temperature over 3 h. Then 10% aqueous potassium sodium tartrate tetrahydrate (Rochelle's Salt) (30 mL) and EtOAc (30 mL) were added and the solution stirred at room temperature over 30 minutes. The organic layer was separated and then dried (Na2SO4) and concentrated to afford 674 mg of t-butyl 3-(hydroxymethyl)azetidine-1-carboxylate (1-3) as a crude product (clear oil). The product was used directly in the next step without purification.

Workup

  1. temperatureThe reaction was warmed to room temperature over 3 h
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-95f7646c3828436ca9bec9e8800a72bb
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

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