[2-(3-cyclopropyl-1-hydroxy-1-trifluoromethyl-prop-2-ynyl)-4-(2-methoxy-ethoxymethoxy)-phenyl]-carbamic Acid Tert-Butyl Ester → 4-Cyclopropylethynyl-6-(2-methoxy-ethoxymethoxy)-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one

HRID 29013Notes

Reaction equation

HRID 29013 reaction equation
C([O:5][C:6](=[O:32])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])=[CH:10][C:9]=1[C:21](O)([C:27]([F:30])([F:29])[F:28])[C:22]#[C:23][CH:24]1[CH2:26][CH2:25]1)(C)(C)C.C([Li])CCC>C1(C)C=CC=CC=1>[CH:24]1([C:23]#[C:22][C:21]2([C:27]([F:30])([F:28])[F:29])[O:5][C:6](=[O:32])[NH:7][C:8]3[CH:13]=[CH:12][C:11]([O:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])=[CH:10][C:9]2=3)[CH2:26][CH2:25]1

Participants

4

Reactant 2

HCID 68800268[2-(3-cyclopropyl-1-hydroxy-1-trifluoromethyl-prop-2-ynyl)-4-(2-methoxy-ethoxymethoxy)-phenyl]-carbamic Acid Tert-Butyl EsterHCID 178418339Butyllithium

Product 1

HCID 688005564-Cyclopropylethynyl-6-(2-methoxy-ethoxymethoxy)-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-oneYield 96.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To 1.2 g (2.6 mmol) of 7 was added 15 mL of toluene, and the reaction mixture was cooled to 0° to −4° C. under argon atmosphere. To the reaction mixture 1.4 mL (3.5 mmol) of n-butyl lithium (2.5M in hexane) was added, and the resulting reaction mixture was allowed to stir at 0° to −4° C. for 10 minutes, warmed up to room temperature, and allowed to reflux for 1 hour. The reaction mixture was concentrated. Then 20 mL of water was added and the aqueous layer was extracted with 4×20 mL of dichloromethane. Organic layers were combined, dried (Na2SO4), and concentrated. The residue was purified by silica gel flash column chromatography using 20% ethyl acetate in hexane to give 965 mg (2.5 mmol, 96%) of 8 as a light brown oil [LC-MS; M+H 386.1].

Workup

  1. temperaturethe reaction mixture was cooled to 0° to −4° C. under argon atmosphere
  2. customthe resulting reaction mixture
  3. temperatureto reflux for 1 hour
  4. concentrationThe reaction mixture was concentrated
  5. additionThen 20 mL of water was added
  6. extractionthe aqueous layer was extracted with 4×20 mL of dichloromethane
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-cf52e11f495a485499f2e6a122f7e3d7
Source dataset
uspto-grants-2008_09
Patent number
US07420043B2

Reaction notes

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