Potassium Hydroxide → HCID 58985888, compound

HRID 1173070Notes

Reaction equation

HRID 1173070 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])[C:10]([C:22]2[O:23][C:24]([C:37](C)(C)[O:38][SiH2]C(C)(C)C)=[CH:25][C:26](=[O:36])[C:27]=2[O:28][Si](C(C)(C)C)(C)C)=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-].[OH-].[K+].[CH3:66][O:67][C:68]1[CH:75]=[CH:74][C:71]([CH2:72]Cl)=[CH:70][CH:69]=1>C1COCC1.CO.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])[C:10]([C:22]2[O:23][C:24]([CH2:37][OH:38])=[CH:25][C:26](=[O:36])[C:27]=2[O:28][CH2:72][C:71]2[CH:74]=[CH:75][C:68]([O:67][CH3:66])=[CH:69][CH:70]=2)=[CH:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 14797Potassium HydroxideHCID 699934-Methyloxybenzyl chlorideHCID 2724141Tetrabutylammonium FluorideHCID 131728522HCID 131728522, compound

Product 1

HCID 58985888HCID 58985888, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Intermediate 204 (191 mg, 0.350 mmol) was dissolved in anhydrous THF (2 mL). TBAF (1 M, 0.7 mL) was added dropwise. The solution was stirred at room temperature overnight. The mixture was extracted with EtOAc. The organic phase was combined and washed with water and brine. The organic layer was dried over Na2SO4 then solvent removed under vacuum. The resulting 3-(3-hydroxy-6-hydroxymethyl-4-oxo-4H-pyran-2-yl)-7-(3-methyl-but-2-enyl)-indole-1-carboxylic acid tert-butyl ester (211) was directly protected as following. KOH (85%, 15 mg, 0.23 mmol) was powdered and dissolved in anhydrous MeOH (3 mL). Then crude 211 was added, followed by p-methoxybenzyl chloride (47 mg, 0.30 mmol). The resulting solution was stirred at room temperature overnight. The mixture was diluted with EtOAc then washed with water and brine. The organic layer was dried over Na2SO4 then solvent removed under vacuum. After flash column chromatography, the desired product was obtained as a yellow oil (70 mg, 43%). 1H NMR (CDCl3): δ 1.61 (9H, s), 1.71 (3H, s), 1.73 (3H, s), 3.71 (3H, s), 3.75 (2H, d, J=6.6 Hz), 4.28 (2H, s), 5.24 (2H, s), 5.25 (1H, m), 6.57 (1H, s), 6.70 (2H, m), 7.08 (2H, m), 7.2-7.3 (2H, m), 7.86 (1H, m), 8.11 (1H, s). 13C NMR (CDCl3): δ 19.1, 22.6, 28.6, 31.3, 33.7, 56.0, 61.9, 73.3, 85.1, 111.4, 114.3, 119.3, 123.1, 124.5, 126.7, 127.3, 129.2, 129.5, 130.9, 133.2, 133.6, 134.5, 137.7, 141.2, 149.4, 149.8, 160.9, 165.1, 175.5. IR (KBr): 3167, 2871, 1554, 1233, 1105 cm−1. HRMS (El): m/z Calcd. for C32H35NO7 [M+] 545.2414, found 545.2429.

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. customsolvent removed under vacuum
  5. additionThen crude 211 was added
  6. stirringThe resulting solution was stirred at room temperature overnight
  7. washthen washed with water and brine
  8. dry with materialThe organic layer was dried over Na2SO4
  9. customsolvent removed under vacuum

Sources & evidence

ORD record
ord-c5720e3f53eb434ea98fc7a156eaec83
Source dataset
uspto-grants-2010_11
Patent number
US07834050B2

Reaction notes

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