2-(4-Chloro-2-iodophenyl)-4,4-dimethyl-4,5-dihydrooxazole → tert-Butyl 3-(5-chloro-2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)phenyl)-3-oxopropyl(methyl)carbamate

HRID 426065Notes

Reaction equation

HRID 426065 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][CH2:10][C:11]([CH3:14])([CH3:13])[N:12]=2)=[C:4](I)[CH:3]=1.C([Li])CCC.CON(C)[C:24](=[O:36])[CH2:25][CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][CH2:10][C:11]([CH3:14])([CH3:13])[N:12]=2)=[C:4]([C:24](=[O:36])[CH2:25][CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33])[CH:3]=1

Participants

5

Reactant 3

HCID 122201312-(4-Chloro-2-iodophenyl)-4,4-dimethyl-4,5-dihydrooxazoleHCID 59364357Tert-butyl 3-(methoxy(methyl)amino)-3-oxopropyl(methyl)carbamateHCID 178418339Butyllithium

Product 1

HCID 59364350tert-Butyl 3-(5-chloro-2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)phenyl)-3-oxopropyl(methyl)carbamateYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(4-chloro-2-iodophenyl)-4,4-dimethyl-4,5-dihydrooxazole (3.3 g, 9.7 mmol) in dry THF (30 mL) at −78° C. was added n-butyl lithium (2.5 M in hexane, 4.0 mL, 10.0 mmol) drop wise. After stirring for 30 min, a solution of tert-butyl 3-(methoxy(methyl)amino)-3-oxopropyl(methyl)carbamate (2.0 g, 8.1 mmol) in dry THF (5 mL) was added. The reaction mixture was warmed slowly to 0° C. then stored in refrigerator (4° C.) over night. The reaction was then warmed to room temperature and stirred 7 h. The reaction was quenched with 1N HCl, diluted with brine and ethyl acetate. After separation, the organic phases were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (120 g column, 0% ethyl acetate in hexanes to 50% ethyl acetate in hexanes) to give product (1.2 g, 38%). 1H NMR (CD3OD) δ 7.75 (d, J=7.6 Hz, 1H), 7.55-7.60 (m, 2H), 4.10-4.20 (m, 2H), 3.58 (t, J=6.8 Hz, 2H), 3.05-3.15 (m, 2H), 2.88 (s, 3H), 1.43 (s, 9H), 1.35 (s, 6H); MS EI m/z 395 (M+H)+.

Workup

  1. waitthen stored in refrigerator (4° C.) over night
  2. temperatureThe reaction was then warmed to room temperature
  3. stirringstirred 7 h
  4. customThe reaction was quenched with 1N HCl
  5. additiondiluted with brine and ethyl acetate
  6. customAfter separation
  7. dry with materialthe organic phases were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography on silica gel (120 g column, 0% ethyl acetate in hexanes to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-05e1eeac0cee4f008139101d36b181d6
Source dataset
uspto-grants-2012_01
Patent number
US08106221B2

Reaction notes

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