Tributylphosphine → 5-(benzyloxy)-1'-[(5-chloro-2-thienyl)methyl]spiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

HRID 2385143Notes

Reaction equation

HRID 2385143 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12](O)=[C:13]([C:15]2([CH2:32][OH:33])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]([CH2:24][C:25]3[S:26][C:27]([Cl:30])=[CH:28][CH:29]=3)[C:16]2=[O:31])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(P(CCCC)CCCC)CCC.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[O:33][CH2:32][C:15]3([C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[N:17]([CH2:24][C:25]4[S:26][C:27]([Cl:30])=[CH:28][CH:29]=4)[C:16]3=[O:31])[C:13]=2[CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 13831TributylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 673797413-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chloro-2-thienyl)methyl]-3-hydroxymethyl-1,3-dihydro-2H-indol-2-one

Product 1

HCID 461943035-(benzyloxy)-1'-[(5-chloro-2-thienyl)methyl]spiro[1-benzofuran-3,3'-indol]-2'(1'H)-oneYield 90.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-[5-(benzyloxy)-2-hydroxyphenyl]-1-[(5-chloro-2-thienyl)methyl]-3-hydroxymethyl-1,3-dihydro-2H-indol-2-one (2.71 g, 5.52 mmol) in anhydrous tetrahydrofuran (60 mL) was added dropwise tributylphosphine (1.39 g, 6.90 mmol). The solution was cooled to 0° C. and di-tert-butyl azodicarboxylate (1.59 g, 6.90 mmol) was added. The solution was stirred at 0° C. for 20 min then quenched with aqueous 10% hydrochloric acid (50 mL). The aqueous solution was extracted with ethyl acetate (3×100 mL), brine (3×50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by flash column chromatography with ethyl acetate in hexanes (20%) to give 5-(benzyloxy)-1′-[(5-chloro-2-thienyl)methyl]spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (2.36 g, 90%) as a colorless solid: mp 132-135° C.; 1H NMR (300 MHz, DMSO-d6) 7.33-7.21 (m, 7H), 7.16-7.12 (m, 2H), 7.02 (ddd, J=7.4, 7.4, 1.0 Hz, 1H), 6.97 (d, J=3.8 Hz, 1H), 6.90-6.32 (m, 2H), 6.21 (d, J=2.3 Hz, 1H), 5.05 (ABq, 2H), 4.82 (s, 2H), 4.72 (ABq, 2H); 13C NMR (75 MHz, DMSO-d6) δ176.6, 155.0, 153.6, 141.9, 138.6, 137.4, 132.0 130.3, 129.4, 128.8, 128.2, 128.1, 127.9, 127.1, 124.3, 123.8, 116.6, 110.8, 110.0, 109.9, 79.4, 70.4, 58.1, 38.9; MS (ES+) m/z 476.3 (M+1), 474.3 (M+1).

Workup

  1. customthen quenched with aqueous 10% hydrochloric acid (50 mL)
  2. extractionThe aqueous solution was extracted with ethyl acetate (3×100 mL), brine (3×50 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo to dryness
  6. customThe residue was purified by flash column chromatography with ethyl acetate in hexanes (20%)

Sources & evidence

ORD record
ord-f905e21c605e491c803b91ca1f426420
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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