Cyclobutanone → Tert-butyl [2-(1-hydroxycyclobutyl)phenyl]carbamate

HRID 458553Notes

Reaction equation

HRID 458553 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[Li]C(C)(C)C.[C:20]1(=[O:24])[CH2:23][CH2:22][CH2:21]1>CCOCC>[C:1]([O:5][C:6](=[O:14])[NH:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=1[C:20]1([OH:24])[CH2:23][CH2:22][CH2:21]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 14496CyclobutanoneHCID 137930t-Butyl carbanilateHCID 178418306HCID 178418306, compound

Product 1

HCID 18442665Tert-butyl [2-(1-hydroxycyclobutyl)phenyl]carbamateYield 32%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To phenyl-carbamic acid tert-butyl ester (2 g, 10.4 mmol) in ether (30 mL) at 0° C. was added t-BuLi (15 mL, 26 mmol, 1.7 M) and the reaction solution stirred for 3 hours prior to the addition of cyclobutanone (1.2 mL, 15.6 mmol). The reaction mixture was allowed to warm to room temperature. Upon completion by thin-layer chromatography (TLC), the reaction was poured into ice-cold saturated ammonium chloride (100 mL) and extracted with ethyl acetate (50 mL). The organics were dried over sodium sulfate, concentrated, and purified on a silica gel column (10% ethyl acetate/hexane) to give tert-butyl[2-(1-hydroxycyclobutyl)phenyl]carbamate (0.86 g, 32%) as a white solid. 1H NMR (DMSO-d6): δ 8.48 (s, 1H), 7.8 (d, 1H, J=7.92 Hz), 7.35 (dd, 1H, J=7.7, 1.4 Hz), 7.25 (td, 1H, J=7.5, 1.6 Hz), 7.03 (td, 1H, J=7.5, 1.3 Hz), 2.51–2.49 (m, 2H), 2.43–2.39 (m, 2H), 2.28–2.25 (m, 2H), 1.45 (s, 9H). MS (ESI) m/z 190 ([M+H]+); MS (ESI) m/z 188 ([M−H]−);

Workup

  1. extractionextracted with ethyl acetate (50 mL)
  2. dry with materialThe organics were dried over sodium sulfate
  3. concentrationconcentrated
  4. custompurified on a silica gel column (10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9f4fba2c09ad43a5ae7e32b18a3e574d
Source dataset
uspto-grants-2007_03
Patent number
US07192956B2

Reaction notes

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