Tetrahydrofuran → HCID 69215938, compound

HRID 1296503Notes

Reaction equation

HRID 1296503 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([OH:6])=O.[CH2:12]([Mg]Br)[CH3:13].C1N=CN([C:21](N2C=NC=C2)=[O:22])C=1.[CH2:28]1COC[CH2:29]1>>[CH2:28]([C:4]1([CH2:12][CH3:13])[C:3]2[C:7]([F:11])=[CH:8][CH:9]=[CH:10][C:2]=2[NH:1][C:21](=[O:22])[O:6]1)[CH3:29]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 682631,1'-CarbonyldiimidazoleHCID 5211422-Amino-6-fluorobenzoic acidHCID 178418443HCID 178418443, compound

Product 1

HCID 69215938HCID 69215938, compoundYield 43%

Procedure

To a stirred solution of 2-amino-6-fluorobenzoic acid (15.34 g, 98.90 mmol) in THF (330 mL) at 0° C. was slowly added ethyl magnesium bromide (650 mL, 650.0 mmol) and allowed to warm to room temperature. After 3 days, the reaction was quenched with chilled ammonium chloride solution (sat.) and extracted several times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated. The crude material was taken up in THF (300 mL) and CDI (14.97 g, 92.30 mmol) was added. The reaction was stirred overnight at room temperature and partitioned between ammonium chloride solution (sat.) and ethyl acetate. The organic layer was washed with 1N HCl and dried over magnesium sulfate. Trituration with ether gave 4,4-diethyl-5-fluoro-1,4-dihydro-2H-3,1-benzoxazin-2-one as an off-white solid (9.57 g, 43%). 1H NMR (DMSO-d6): δ 10.33 (s, 1H), 7.31 (m, 1H), 6.86 (m, 1H), 6.73 (d, J=8.0 Hz, 1H), 2.08 (m, 2H), 1.90 (m, 2H), 0.80 (t, J=7.2 Hz, 6H); MS (ESI) m/z 224 ([M+H]+); MS (ESI) m/z 222 ([M−H]−); Anal. calcd for C12H14FNO2: C, 64.56; H, 6.32; N, 6.27. Found: C, 64.64; H, 6.27 N, 6.16.

Workup

  1. customat 0° C.
  2. customthe reaction was quenched with chilled ammonium chloride solution (sat.)
  3. extractionextracted several times with ethyl acetate
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. concentrationconcentrated
  6. custompartitioned between ammonium chloride solution (sat.) and ethyl acetate
  7. washThe organic layer was washed with 1N HCl
  8. dry with materialdried over magnesium sulfate

Sources & evidence

ORD record
ord-8c920e862ab64e2aaafab17848efa9b0
Source dataset
uspto-grants-2007_07
Patent number
US07247625B2

Reaction notes

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