4-Methylmorpholine → HCID 22728145, compound

HRID 2086154Notes

Reaction equation

HRID 2086154 reaction equation
[CH3:1][C:2]1[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[CH:17]=[C:16]([CH3:23])[C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([O:14][CH3:15])=[C:9]([CH:13]=1)[C:10]([OH:12])=O.CN1CCOCC1.ClC(OCC(C)C)=O.[CH:39]1([NH2:43])[CH2:42][CH2:41][CH2:40]1>O1CCCC1>[CH:39]1([NH:43][C:10](=[O:12])[C:9]2[CH:13]=[C:5]([O:4][C:3]3[C:16]([CH3:23])=[CH:17][C:18]([N+:20]([O-:22])=[O:21])=[CH:19][C:2]=3[CH3:1])[CH:6]=[CH:7][C:8]=2[O:14][CH3:15])[CH2:42][CH2:41][CH2:40]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 75645CyclobutylamineHCID 22728132HCID 22728132, compound

Product 1

HCID 22728145HCID 22728145, compoundYield 71.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(2,6-Dimethyl-4-nitro-phenoxy)-2-methoxy-benzoic acid (2.0 g, 6.3 mmol) in tetrahydrofuran (60 mL) at 0° C. under nitrogen was added N-methylmorpholine (1.4 mL) and isobutyl chloroformate (1.3 g, 9.5 mmol). The resulting mixture was stirred for 25 minutes at 0° C., and cyclobutyl amine (0.9 g, 13 mmol) was added in a single portion at 0° C. The reaction solution was stirred for another 30 minutes at 0° C. and warmed to room temperature over 1 hour. The solution was then concentrated to a viscous oily solid which was partitioned between water (25 mL) and methylene chloride (25 mL). The organic phase was separated and the aqueous phase was extracted with methylene chloride (10 mL). The combined organic extracts were washed with saturated aqueous NaHCO3, 1N hydrochloric acid and brine, dried over Na2SO4, filtered, and concentrated. To the residue was purified by column chromatography (Et2O/methylene chloride/hexane=1/7/12) to afford the title compound (1.67 grams) as a crude product. 1H NMR (400 MHz, CDCl3) δ8.04 (br s, 1H), 7.98 (s, 2H), 7.54 (d, 1H), 6.90 (d, 1H), 6.86 (dd, 1H), 4.51-4.49 (m, 1H), 3.94 (s, 3H), 2.41-2.38 (m, 2H), 2.17 (s, 6H), 1.95-1.90 (m, 2H), 1.80-1.75 (m, 2H). MS (APCI+) Calc: 370.4, Found: 371.2 (M+1).

Workup

  1. stirringThe reaction solution was stirred for another 30 minutes at 0° C.
  2. temperaturewarmed to room temperature over 1 hour
  3. concentrationThe solution was then concentrated to a viscous oily solid which
  4. customwas partitioned between water (25 mL) and methylene chloride (25 mL)
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted with methylene chloride (10 mL)
  7. washThe combined organic extracts were washed with saturated aqueous NaHCO3, 1N hydrochloric acid and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customTo the residue was purified by column chromatography (Et2O/methylene chloride/hexane=1/7/12)

Sources & evidence

ORD record
ord-c9cd3e694a244d5fbcfd4234a5357dd6
Source dataset
uspto-grants-2004_04
Patent number
US06723744B2

Reaction notes

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