4-Phenylbutyric Acid → HCID 24983523, compound

HRID 1676277Notes

Reaction equation

HRID 1676277 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[F:28][C:29]1[CH:30]=[C:31]([CH:33]=[CH:34][C:35]=1[O:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39]2[CH:43]=[CH:44][S:45][C:38]=12)[NH2:32]>C1COCC1>[F:28][C:29]1[CH:30]=[C:31]([NH:32][C:10](=[O:12])[CH2:9][CH2:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:33]=[CH:34][C:35]=1[O:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39]2[CH:43]=[CH:44][S:45][C:38]=12

Participants

6

Reactant 4

HCID 47754-Phenylbutyric AcidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 594244303-Fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)aniline

Product 1

HCID 24983523HCID 24983523, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 4-phenylbutanoic acid (49 mg, 0.3 mmol) in 1 mL THF at −78° C. under nitrogen was added N-methyl morpholine (66 μL, 0.6 mmol) followed by isobutyl chloroformate (34 μL, 0.26 mmol). After 15 minutes, a solution of 3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)aniline (Example 1, Step B) in 1 mL THF was added and the reaction mixture was warmed to reflux. After refluxing overnight, the reaction was cooled to room temperature and partitioned between CH2Cl2 (30 mL) and 10% citric acid (30 mL). The organics were isolated and washed 1×30 mL with 10% citric acid and 2×30 mL with saturated NaHCO3. The organics were dried (MgSO4), filtered, concentrated and loaded onto a Biotage 12S column with 2/3 EtOAc/hexanes and eluted. The fractions containing the product were pooled and concentrated to a white foam (63 mg, 77%). 1H NMR (400 MHz, CDCl3) δ 8.48 (d, 1H), 7.75 (d, 1H), 7.73 (m, 1H), 7.69 (br s, 1H), 7.55 (d, 1H), 7.29 (m, 2H), 7.20 (m, 5H), 6.50 (d, 1H), 2.72 (m, 2H), 2.38 (m, 2H), 2.09 (m, 2H). LRMS (ESI pos) m/e 407.0 (M+1).

Workup

  1. temperaturethe reaction mixture was warmed to reflux
  2. temperatureAfter refluxing overnight
  3. custompartitioned between CH2Cl2 (30 mL) and 10% citric acid (30 mL)
  4. customThe organics were isolated
  5. washwashed 1×30 mL with 10% citric acid and 2×30 mL with saturated NaHCO3
  6. dry with materialThe organics were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washeluted
  10. additionThe fractions containing the product
  11. concentrationconcentrated to a white foam (63 mg, 77%)

Sources & evidence

ORD record
ord-4ba84c4e8a3e44889dadb0e454665df7
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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