tert-Butanol → (2-Bromo-5-methoxy-3-methyl-phenyl)-carbamic acid tert-butyl ester

HRID 723166Notes

Reaction equation

HRID 723166 reaction equation
[Br:1][C:2]1[C:10](C)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][C:3]=1[C:4](O)=O.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:21])=CC=1.C([N:34]([CH:37](C)C)CC)(C)C.[C:40]([OH:44])([CH3:43])([CH3:42])[CH3:41]>>[C:40]([O:44][C:37](=[O:21])[NH:34][C:10]1[CH:9]=[C:8]([O:12][CH3:13])[CH:7]=[C:3]([CH3:4])[C:2]=1[Br:1])([CH3:43])([CH3:42])[CH3:41]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 152273622-Bromo-5-methoxy-3-methylbenzoic acid

Product 1

HCID 69586528(2-Bromo-5-methoxy-3-methyl-phenyl)-carbamic acid tert-butyl esterYield 70%

Conditions

Temperature
80 °C

Procedure

A solution of 2-bromo-5-methoxy-3-methyl-benzoic acid ((Example 198: step a) 3.39 g, 13.8 mmol) in dry tert-butanol was treated with DPPA (3.58 mL, 16.6 mmol) dropwise and stirred 5 min. The solution was treated with diisopropylethylamine (2.89 mL, 16.6 mmol) and heated to 80° C. 17.5 h. Tert-butanol was removed in vacuo. The residue was taken up in EtOAc and washed with saturated aqueous NaHCO3 (2×60 mL) and water (1×60 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Silica gel chromatography (10% EtOAc in hexanes) afforded the product (2-bromo-5-methoxy-3-methyl-phenyl)-carbamic acid tert-butyl ester (3.05 g, 70%) as a colorless oil. 1H NMR (CDCl3): δ 7.701 (d, 1H, J=1.6 Hz), 7.146 (s, NH), 6.517 (d, 1H, J=3.2 Hz), 3.797 (s, 3H), 2.360 (s, 3H), 1.534 (s, 9H).

Workup

  1. custom17.5 h
  2. customTert-butanol was removed in vacuo
  3. washwashed with saturated aqueous NaHCO3 (2×60 mL) and water (1×60 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4e004caf5dab4eeabe50388c255ff53a
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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