Cesium carbonate → 6-[1-(diphenylmethyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-5-hydroxy-3-methyl-1,3-benzoxazol-2(3H)-one

HRID 1965485Notes

Reaction equation

HRID 1965485 reaction equation
[C:1]1([CH:7]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]([C:17]3[C:28]([OH:29])=[CH:27][C:20]4[N:21]([CH3:26])[C:22](=[O:25])C[O:24][C:19]=4[CH:18]=3)[C:9]2=[O:30])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCI>O1CCCC1>[C:1]1([CH:7]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]([C:17]3[C:28]([OH:29])=[CH:27][C:20]4[N:21]([CH3:26])[C:22](=[O:25])[O:24][C:19]=4[CH:18]=3)[C:9]2=[O:30])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11644ChloroiodomethaneHCID 686010007-[1-(diphenylmethyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-6-hydroxy-4-methyl-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 673573586-[1-(diphenylmethyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-5-hydroxy-3-methyl-1,3-benzoxazol-2(3H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 7-[1-(diphenylmethyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-6-hydroxy-4-methyl-2H-1,4-benzoxazin-3(4H)-one (3.4 g, 7.1 mmol) in anhydrous tetrahydrofuran (30 mL) was deoxygenated for 1 h with dry argon. Cesium carbonate (8.1 g, 25 mmol) and chloroiodomethane (1.5 mL, 21 mmol) were added and the heterogeneous reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was filtered through a pad of diatomaceous earth and the pad was washed with ethyl acetate (50 mL). The filtrate was concentrated in vacuo and the crude product was purified by column chromatography with ethyl acetate in hexanes (10% to 70% gradient) to afford 6-[1-(diphenylmethyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-5-hydroxy-3-methyl-1,3-benzoxazol-2(3H)-one. To a solution containing 641-(diphenylmethyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-5-hydroxy-3-methyl-1,3-benzoxazol-2(3H)-one (1.0 g, 20 mmol), in trifluoroacetic acid (10 mL) was added triethylsilane (1.6 mL, 10 mmol) and the reaction mixture was heated at reflux for 16 h. The reaction mixture was concentrated in vacuo and the crude product was purified by column chromatography with ethyl acetate in hexanes (10% to 60% gradient) to afford 4-methyl-4,7-dihydrospiro[benzofuro[5,6-b][1,4]oxazine-8,3′-indoline]-2′,3(2H)-dione (0.52 g, 78%) as an off-white solid: mp>250° C.; 1H NMR (300 MHz, DMSO-d6) δ10.63 (s, 1H), 7.28-7.23 (m, 1H), 7.10 (d, J=7.1 Hz, 1H), 6.99-6.90 (m, 2H), 6.87 (s, 1H), 6.36 (s, 1H), 4.81 (d, J=9.3 Hz, 1H), 4.70 (d, J=9.3 Hz, 1H), 4.51 (s, 2H), 3.26 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ178.0, 164.4, 156.0, 141.7, 139.2, 132.2, 130.7, 128.8, 123.7, 123.0, 122.2, 110.8, 109.8, 97.8, 79.7, 67.0, 57.6, 28.1; MS (ES−) m/z 321.2 (M−1).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of diatomaceous earth
  2. washthe pad was washed with ethyl acetate (50 mL)
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe crude product was purified by column chromatography with ethyl acetate in hexanes (10% to 70% gradient)

Sources & evidence

ORD record
ord-6ef8a62792ec4f16b9c69a116ccf842e
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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