Triethylamine → Ethyl 7-[({[(2S)-1'-{2-[(5R)-3-[3,5-bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)(methyl)amino]heptanoate

HRID 446562Notes

Reaction equation

HRID 446562 reaction equation
[F:1][C:2]([F:49])([F:48])[C:3]1[CH:4]=[C:5]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[C:6]([N:8]1[CH2:12][C@@:11]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]3([C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36]CC(O)=O)[CH2:24][CH2:23]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:10][CH2:9]1)=[O:7].[CH2:50]([N:52]([CH2:55][CH3:56])[CH2:53][CH3:54])C.ClC(OCC(C)C)=[O:59].CNCC[CH2:69][CH2:70][CH2:71][CH2:72][C:73]([O:75][CH2:76][CH3:77])=[O:74].C(=O)([O-])O.[Na+]>ClCCl>[F:47][C:44]([F:45])([F:46])[C:42]1[CH:41]=[C:5]([CH:4]=[C:3]([C:2]([F:49])([F:48])[F:1])[CH:43]=1)[C:6]([N:8]1[CH2:12][C@@:11]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]3([C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH2:54][C:53]([N:52]([CH3:50])[CH2:55][CH2:56][CH2:69][CH2:70][CH2:71][CH2:72][C:73]([O:75][CH2:76][CH3:77])=[O:74])=[O:59])[CH2:24][CH2:23]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:10][CH2:9]1)=[O:7]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 86663420HCID 86663420, compoundHCID 86663458Ethyl 7-(methylamino)heptanoate

Product 1

HCID 86663457Ethyl 7-[({[(2S)-1'-{2-[(5R)-3-[3,5-bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)(methyl)amino]heptanoateYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The compound (625 mg, 0.901 mmol) obtained in Example 1j was dissolved in dichloromethane (9 mL), triethylamine (0.376 mL, 2.70 mmol) and isobutyl chloroformate (183 μL, 1.35 mmol) were added under ice cooling, and the mixture was stirred at the same temperature. The compound (467 mg, 2.70 mmol) obtained in Example 68a was added under ice cooling, and then the temperature was increased to room temperature. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with dichloromethane (×2). The resulting organic layer was dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (a elution solvent, ethyl acetate) to give the title compound (615 mg; yield, 79%).

Workup

  1. extractionthe mixture was extracted with dichloromethane (×2)
  2. dry with materialThe resulting organic layer was dried with anhydrous sodium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customThe resulting residue was purified by NH silica gel column chromatography (a elution solvent, ethyl acetate)

Sources & evidence

ORD record
ord-df1a81ab01114d1293e99b34a2462de2
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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