Benzyl chloroformate → Benzyl 3-hydroxyazetidine-1-carboxylate

HRID 541017Notes

Reaction equation

HRID 541017 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([OH:6])[CH2:3]1.C([O-])([O-])=O.[K+].[K+].Cl[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15]>O.C1COCC1>[CH2:17]([O:16][C:14]([N:2]1[CH2:5][CH:4]([OH:6])[CH2:3]1)=[O:15])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 27592903-Hydroxyazetidine hydrochloride

Product 1

HCID 10081755Benzyl 3-hydroxyazetidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22.5 °C

Procedure

To a solution of azetidin-3-ol hydrochloride 7 (25 g, 0.23 mol) in water (150 mL) and THF (300 mL) was added K2CO3 (63.1 g, 0.46 mol). The mixture was stirred for 30 min. at 20-25° C. Then benzyl chloroformate (40.9 g, 0.24 mol) was added within 30 min. at 0-5° C. followed by stirring the mixture overnight at 20-25° C. THF was removed on a rotavap at 30° C./vacuum and the mixture was extracted with ethyl acetate (2×150 mL). The combined organic layer was washed with water (1×50 mL), dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate-heptanes 1:1 and 4:1 to yield 8 as a clear oil (47.3 g, 100%). 1H NMR (300 MHz, CDCl3): δ 3.72 (1H, d, J=6.2 Hz), 3.85 (2H, dd, J=9.5, 4.4 Hz), 4.17 (2H, dd, J=9.5, 6.7 Hz), 4.49-4.57 (1H, m), 5.06 (2H, s), 7.31-7.38 (5H, m); 13C NMR (75 MHz, CDCl3): δ 59.2, 61.6, 66.9, 127.9, 128.1, 128.5, 136.5, 156.6; IR: (film) 3406, 1686, 1438 cm−1; ES-HRMS m/z: (M++1H) calcd. for C11H14NO3 208.0968. found 208.0967.

Workup

  1. stirringby stirring the mixture overnight at 20-25° C
  2. customTHF was removed on a rotavap at 30° C./vacuum
  3. extractionthe mixture was extracted with ethyl acetate (2×150 mL)
  4. washThe combined organic layer was washed with water (1×50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with ethyl acetate-heptanes 1:1 and 4:1

Sources & evidence

ORD record
ord-34c79ee81c7e42828ec0be8b5d7c858b
Source dataset
uspto-grants-2014_10
Patent number
US08871938B2

Reaction notes

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