tert-Butanol → (3-o-Tolyl-isoxazol-4-yl)-carbamic acid tert-butyl ester

HRID 474365Notes

Reaction equation

HRID 474365 reaction equation
[C:1]1([CH3:15])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:11](C(O)=O)=[CH:10][O:9][N:8]=1.C1C=CC(OP([O:28][C:29]2C=CC=CC=2)(N=[N+]=[N-])=O)=CC=1.C([N:37](CC)CC)C.[C:42]([OH:46])([CH3:45])([CH3:44])[CH3:43]>>[C:42]([O:46][C:29](=[O:28])[NH:37][C:11]1[C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[CH3:15])=[N:8][O:9][CH:10]=1)([CH3:45])([CH3:44])[CH3:43]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 666771273-o-Tolyl-isoxazole-4-carboxylic acid

Product 1

HCID 58063348(3-o-Tolyl-isoxazol-4-yl)-carbamic acid tert-butyl esterYield 75%

Conditions

Temperature
85 °C

Procedure

A mixture of 3-o-tolyl-isoxazole-4-carboxylic acid (930 mg, 4.58 mmol, 1.0 equiv), diphenylphosphonic azide (1.26 g, 4.58 mmol, 1.0 equiv) and triethylamine (463 mg, 4.58 mmol, 1.0 equiv) in tert-butanol (40 mL) was heated to 85° C. for 16 hours. The mixture was concentrated under vacuum and the residue taken up into ethyl acetate and sequentially washed with 1M HCl aqueous solution, saturated aqueous sodium bicarbonate solution, water, and saturated aqueous sodium chloride solution. The collected organic was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel (gradient: 0 to 15% ethyl acetate in cyclohexane) to afford 943 mg (75%) of (3-o-tolyl-isoxazol-4-yl)-carbamic acid tert-butyl ester. LCMS (ESI) m+H=275.0; 1H NMR (300 MHz, CDCl3) δ: 8.92 (s, 1H), 7.47-7.29 (m, 4H), 5.87 (s, 1H), 2.29 (s, 3H), 1.48 (s, 9H).

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. washsequentially washed with 1M HCl aqueous solution, saturated aqueous sodium bicarbonate solution, water, and saturated aqueous sodium chloride solution
  3. dry with materialThe collected organic was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by flash column chromatography on silica gel (gradient: 0 to 15% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-ed6a5f401fc145609ca72ec4839848de
Source dataset
uspto-grants-2014_01
Patent number
US08637526B2

Reaction notes

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