Benzyl Alcohol → Benzyl [1-(3-methoxyphenyl)-1-methylethyl]carbamate

HRID 1041485Notes

Reaction equation

HRID 1041485 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]([CH3:14])([CH3:13])C(O)=O)[CH:6]=[CH:7][CH:8]=1.C1(C)C=CC=CC=1.C([N:24]([CH2:27]C)CC)C.C1C=CC([O:35]P(OC2C=CC=CC=2)(N=[N+]=[N-])=O)=CC=1.[CH2:48]([OH:55])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[CH2:48]([O:55][C:27](=[O:35])[NH:24][C:9]([C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)([CH3:13])[CH3:14])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1

Participants

7

Reactant 5

HCID 244Benzyl AlcoholHCID 1140TolueneHCID 8471Triethylamine2×HCID 123414Diphenylphosphoryl azideHCID 108216342-(3-Methoxyphenyl)-2-methylpropanoic acid

Product 1

HCID 67264266Benzyl [1-(3-methoxyphenyl)-1-methylethyl]carbamateYield 96.9%

Reagents, catalysts & solvents 1

HCID 311Citric AcidSolvent

Conditions

Temperature
85 °C

Procedure

Into a round bottom flask, 2-(3-methoxy-phenyl)-2-methyl-propionic acid (15.00 g, 77.23 mmol), toluene (150.0 mL, 1408 mmol) and triethylamine (10.2 mL, 73.4 mmol) were added a room temperature under an atmosphere of Nitrogen. Diphenylphosphonic azide (15.8 mL, 73.4 mmol) was added. The reaction was heated at 85° C. for 3 hours. benzyl alcohol (7.99 mL, 77.2 mmol) and triethylamine (10.2 mL, 73.4 mmol) was added. The reaction was heated to reflux overnight under an atmosphere of Nitrogen. 10% Citric acid (300 mL) was added to the reaction mixture at room temperature. The reaction was extracted with EtOAc (3×250 mL). The combined organic was washed with brine, and dried over magnesium sulfate. The solid was filtered and washed with EtOAc. The solvent was removed under vacuum. The product was isolate via ISCO column chromatography with hexane and EtOAc as eluant (15% EtOAc) to give [1-(3-Methoxy-phenyl)-1-methyl-ethyl]-carbamic acid benzyl ester (21.30 g, 92%). 1H-NMR (DMSO-D6, 400 MHz): δ 7.68 (bs, 1H), 7.25-7.42 (m, 5H), 7.20 (t, 1H), 6.91 (d, 1H), 6.86 (s, 1H), 6.75 (d, 1H), 4.94 (s, 2H), 3.70 (s, 3H), 1.51 (s, 6H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux overnight under an atmosphere of Nitrogen
  3. extractionThe reaction was extracted with EtOAc (3×250 mL)
  4. washThe combined organic was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationThe solid was filtered
  7. washwashed with EtOAc
  8. customThe solvent was removed under vacuum
  9. customThe product was isolate via ISCO column chromatography with hexane and EtOAc as eluant (15% EtOAc)

Sources & evidence

ORD record
ord-3871bd56d11e493783f891f5a801c05c
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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