Sodium Carbonate → tert-butyl N-(4-chloro-3-(hydroxymethyl)phenyl)carbamate

HRID 38673

Reaction equation

HRID 38673 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:10])=[C:6]([CH2:8][OH:9])[CH:7]=1.[C:11](=[O:14])([O-])[O-:12].[Na+].[Na+]>O1CCOCC1.O>[Cl:10][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:11](=[O:14])[O:12][C:6]([CH3:8])([CH3:7])[CH3:5])=[CH:7][C:6]=1[CH2:8][OH:9]

Participants

5

Reactant 2

HCID 10340Sodium CarbonateHCID 13567962(5-Amino-2-chlorophenyl)methanol

Product 1

HCID 54223790tert-butyl N-(4-chloro-3-(hydroxymethyl)phenyl)carbamateYield 136.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (5-amino-2-chlorophenyl)methanol (Aldrich, 500 mg, 3.17 mmol) in a mixture of dioxane (7.5 mL), water (7.5 mL) was added sodium carbonate (336 mg, 3.17 mmol) previously dissolved in 4 mL of water. Solution was stirred and cooled in an ice bath. Boc-anhydride (Aldrich, 692 mg, 3.17 mmol) was added in one portion, and stirring was continued at room temperature for 3 h. Dioxane was removed in vacuo conditions and the aqueous layer chilled, covered with a layer of ethyl acetate, and acidified to pH 4 with dilute KHSO4 (10%, aq) (ALDRICH). This was followed by extraction (EtOAc) and purification by chromatographic column 25 g cartridge (ISOLUTE silice) using Hex/EtOAc 100/0 to 50/50, giving 1,1-dimethylethyl [4-chloro-3-(hydroxymethyl)phenyl]carbamate (560 mg, 2.17 mmol, 68%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.46 (br s, 1H), 7.72 (s, 1H), 7.21-7.32 (m, 2H), 5.35 (t, 1H), 4.48 (d, 2H), 1.47 (s, 9H).

Workup

  1. temperaturecooled in an ice bath
  2. stirringstirring
  3. customDioxane was removed in vacuo conditions
  4. temperaturethe aqueous layer chilled
  5. extractionThis was followed by extraction (EtOAc) and purification by chromatographic column 25 g cartridge (ISOLUTE silice)

Sources & evidence

ORD record
ord-178c23a564744a40a216423d55993ca0
Source dataset
uspto-grants-2013_09
Patent number
US08524750B2

Linked notes

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