Diisopropylethylamine → tert-Butyl [3-(benzyloxy)cyclobutyl]carbamate

HRID 1846754Notes

Reaction equation

HRID 1846754 reaction equation
[CH2:1]([O:8][CH:9]1[CH2:12][CH:11](C(O)=O)[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:23])=CC=1.C([N:36]([CH:39](C)C)CC)(C)C.[CH3:42][C:43]([CH3:46])([O-:45])[CH3:44].[K+]>C1(C)C=CC=CC=1.C1COCC1.O.CCOC(C)=O>[CH2:1]([O:8][CH:9]1[CH2:10][CH:11]([NH:36][C:39](=[O:23])[O:45][C:43]([CH3:46])([CH3:44])[CH3:42])[CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 128151113-(Benzyloxy)cyclobutane-1-carboxylic acidHCID 23665647Potassium tert-butoxide

Product 1

HCID 53415284tert-Butyl [3-(benzyloxy)cyclobutyl]carbamateYield 75%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(benzyloxy)cyclobutanecarboxylic acid (3.40 g, 16.49 mmol), DPPA (4.62 mL, 21.43 mmol), and diisopropylethylamine (3.73 mL, 21.43 mmol) in toluene (35 mL) under argon was warmed to 80° C. and stirred for 7 h, then cooled to RT. The mixture was cooled to 0° C. and then added slowly via canula to a suspension of potassium tert butoxide (3.70 g, 33.0 mmol) in THF (50 mL) under argon held at RT. The mixture was then stirred for 1 h and EtOAc and water were then added. The layers were separated, and the organic layer was dried (MgSO4), filtered, and concentrated to give an oil. The oil was purified by silica gel chromatography (0 to 50% EtOAc/hexane gradient) to give product as a white solid (3.42 g, 75%).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. customheld at RT
  3. stirringThe mixture was then stirred for 1 h
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give an oil
  9. customThe oil was purified by silica gel chromatography (0 to 50% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-654092b370954f62b6ac3cd8c5ffb2a7
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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