Phenol → Carbamic acid, [(2-fluoro-4-phenoxyphenyl)methyl]-, 1,1-dimethylethyl ester

HRID 2041139Notes

Reaction equation

HRID 2041139 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:10]=1[F:16])([CH3:4])([CH3:3])[CH3:2].[C:18]1([OH:24])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.[Cu]Cl>[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:24][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:11][C:10]=1[F:16])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 996PhenolHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 53432589tert-Butyl [(4-bromo-2-fluorophenyl)methyl]carbamate

Product 1

HCID 66706560Carbamic acid, [(2-fluoro-4-phenoxyphenyl)methyl]-, 1,1-dimethylethyl esterYield 58%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

Mix under argon atmosphere (4-bromo-2-fluorobenzyl)-carbamic acid tert-butyl ester (2.12 g, 7.0 mmol), phenol (1.32 g, 14 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (129 mg, 0.7 mmol), and cesium carbonate (4.56 g, 14 mmol) in anhydrous NMP (15 mL). Degas the flask, fill with argon and add copper(I) chloride (346 mg, 3.5 mmol) quickly. Degas the flask then fill with argon and heat at 120° C. for 5 h. Cool to ambient temperature, dilute with EtOAc and filter. Wash the mixture sequentially with 0.5N aqueous HCl, 0.5N aqueous NaOH and brine. Separate the organic layer, dry over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1 and 3:1) to obtain the desired intermediate (1.28 g, 58%). GC-MS m/z: 260 [(M-C4H9)+].

Workup

  1. customDegas the flask
  2. customDegas the flask
  3. temperatureCool to ambient temperature
  4. additiondilute with EtOAc
  5. filtrationfilter
  6. washWash the mixture sequentially with 0.5N aqueous HCl, 0.5N aqueous NaOH and brine
  7. customSeparate the organic layer
  8. dry with materialdry over Na2SO4
  9. concentrationconcentrate in vacuo
  10. customPurify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1 and 3:1)

Sources & evidence

ORD record
ord-79c26fd6a7a14a36adcfd7cbaf9f1be2
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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