4-Methylmorpholine → N-(3,3-dimethylbutyl)-2-(2'-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-1'(2'H)-yl)acetamide

HRID 2385501Notes

Reaction equation

HRID 2385501 reaction equation
[O:1]=[C:2]1[C:10]2([CH2:14][O:13][C:12]3[CH:15]=[C:16]4[C:20](=[CH:21][C:11]2=3)[CH2:19][CH2:18][O:17]4)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:22][C:23]([OH:25])=O.C(OC(Cl)=O)C(C)C.CN1CCOCC1.[CH3:41][C:42]([CH3:47])([CH3:46])[CH2:43][CH2:44][NH2:45]>ClCCl>[CH3:41][C:42]([CH3:47])([CH3:46])[CH2:43][CH2:44][NH:45][C:23](=[O:25])[CH2:22][N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]2([CH2:14][O:13][C:12]3[CH:15]=[C:16]4[C:20](=[CH:21][C:11]2=3)[CH2:19][CH2:18][O:17]4)[C:2]1=[O:1]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 197093,3-DimethylbutylamineHCID 62365Isobutyl chloroformateHCID 59263485(2'-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3-indol]-1'(2'H)-yl)acetic acid

Product 1

HCID 59352706N-(3,3-dimethylbutyl)-2-(2'-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-1'(2'H)-yl)acetamideYield 41.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)acetic acid (0.25 g, 0.74 mmol), isobutylchloroformate (0.11 mL, 0.81 mmol), N-methylmorpholine (0.09 mL, 0.81 mmol) in dichloromethane (10 mL) was added 3,3-dimethylbutylamine (0.11 g, 1.1 mmol). The solution was stirred at ambient temperature for 16 h, diluted with dichloromethane (10 mL) and washed with 2 M sodium carbonate (2×25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by flash chromatography with ethyl acetate in hexanes (30% to 50% gradient) to afford N-(3,3-dimethylbutyl)-2-(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)acetamide (0.13 g, 41%) as a colorless solid: mp 161-163° C.; 1H NMR (300 MHz, DMSO-d6) δ8.14 (dd, J=5.4, 5.4 Hz, 1H), 7.25 (dd, J=7.6, 7.6 Hz, 1H), 7.11 (d, J=6.9 Hz, 1H), 7.03-6.95 (m, 1H), 6.90 (d, J=7.8 Hz, 1H), 6.53 (s, 1H), 6.37 (s, 1H), 4.71 (ABq, 2H), 4.51-4.40 (m, 2H), 4.38-4.20 (m, 2H), 3.12-3.01 (m, 2H), 2.93 (t, J=8.6 Hz, 2H), 1.37-1.27 (m, 2H), 0.85 (s, 9H); 13C NMR (75 MHz, DMSO-d6) δ177.6, 166.3, 161.5, 160.9, 143.1, 132.7, 129.0, 123.8, 123.3, 121.3, 120.2, 119.8, 109.4, 92.8, 80.2, 72.5, 57.3, 43.2, 43.0, 35.9, 30.0, 29.7, 28.8; MS (ES+) m/z 421.2 (M+1).

Workup

  1. washwashed with 2 M sodium carbonate (2×25 mL)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo to dryness
  5. customThe residue was purified by flash chromatography with ethyl acetate in hexanes (30% to 50% gradient)

Sources & evidence

ORD record
ord-b16f379eec4a49dc846b5f32135da932
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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