Water → Ethyl 1-((1-(2-(tert-butyldimethylsilyloxy)ethyl)pyrrolidin-3-yl)methyl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 2061885Notes

Reaction equation

HRID 2061885 reaction equation
Cl.[I:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH:14]1[CH2:18][CH2:17][NH:16][CH2:15]1)[CH:8]=[C:7]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:6]2=[O:24].[Si:25]([O:32][CH2:33][CH:34]=O)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].C([BH3-])#N.[Na+].O>CO>[Si:25]([O:32][CH2:33][CH2:34][N:16]1[CH2:17][CH2:18][CH:14]([CH2:13][N:9]2[C:10]3[C:5](=[CH:4][C:3]([I:2])=[CH:12][CH:11]=3)[C:6](=[O:24])[C:7]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:8]2)[CH2:15]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 962WaterHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 68470833HCID 68470833, compound2×

Product 1

HCID 59415872Ethyl 1-((1-(2-(tert-butyldimethylsilyloxy)ethyl)pyrrolidin-3-yl)methyl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 40.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

Ethyl 6-iodo-4-oxo-1-(pyrrolidin-3-ylmethyl)-1,4-dihydroquinoline-3-carboxylate hydrochloride (Intermediate 126, 500 mg, 1.08 mmol) was suspended in methanol (15 mL) then (tert-butyldimethylsilyloxy)acetaldehyde (1 mL, 5.4 mmol) and sodium cyanoborohydride (612 mg, 9.7 mmol) were added. The reaction was stirred at 23° C. for 16 h. The volume of the reaction was reduced by half and water (25 mL) was added. The suspension was extracted with 2:1 ethyl acetate: tetrahydrofuran (3×, 10 mL). The organic phases were combined, dried over sodium sulfate, and the solvent was removed in vacuo. The residue was chromatographed on a 4 g Analogix column eluting with 0-10% methanol in dichloromethane. The solid was then dried in a vacuum oven at 50° C. for 18 h to give 253 mg (39% yield) of ethyl 1-((1-(2-(tert-butyldimethylsilyloxy)ethyl)pyrrolidin-3-yl)methyl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate as an off white solid.

Workup

  1. additionwas added
  2. extractionThe suspension was extracted with 2:1 ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. customthe solvent was removed in vacuo
  5. customThe residue was chromatographed on a 4 g Analogix column
  6. washeluting with 0-10% methanol in dichloromethane
  7. customThe solid was then dried in a vacuum oven at 50° C. for 18 h

Sources & evidence

ORD record
ord-e4268755e52042e6814d11f625302b3c
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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