Water → HCID 86670470, compound

HRID 1911854Notes

Reaction equation

HRID 1911854 reaction equation
[H-].[Na+].[Si:3]([O:10][C@H:11]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C@H:12]1[CH2:16][CH2:15][C@@H:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24](=[O:27])[NH:25][CH3:26])=[CH:20][CH:19]=2)[N:13]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].Br[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[F:49].O>CN(C=O)C>[Si:3]([O:10][C@H:11]([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C@H:12]1[CH2:16][CH2:15][C@@H:14]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:24](=[O:27])[N:25]([CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=3[F:49])[CH3:26])=[CH:22][CH:23]=2)[N:13]1[C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])([C:6]([CH3:7])([CH3:8])[CH3:9])([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 67968alpha-Bromo-o-fluorotolueneHCID 86670469HCID 86670469, compound

Product 1

HCID 86670470HCID 86670470, compoundYield 99.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (6.1 mg of a 60 wt % dispersion in mineral oil, 0.153 mmol, 1 equivalent) was added to a stirred, room temperature mixture tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-[4-(methylcarbamoyl)benzyl]pyrrolidine-1-carboxylate (80 mg, 0.148 mmol) in DMF (0.74 mL), and the mixture was stirred for 10 minutes. 1-(Bromomethyl)-2-fluorobenzene (0.0281 mg, 0.148 mmol, 1 equivalent) was added and the mixture was stirred overnight. Water was then added and the mixture was partitioned with EtOAc. The aqueous layer was extracted with EtOAc (3×), and the combined organic extracts were washed with brine, dried with Na2SO4, filtered, and concentrated in vacuo. The residue was purified by normal phase flash chromatography using silica gel (0-50% hexanes/ethyl acetate). The product was collected and concentrated in vacuo to afford the title compound (95 mg, 99%). LC-MS=669.2 (M+Na)+.

Workup

  1. stirringthe mixture was stirred overnight
  2. customthe mixture was partitioned with EtOAc
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by normal phase flash chromatography
  9. customThe product was collected
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-19233ad963984d078e357f8113d54d50
Source dataset
uspto-grants-2013_12
Patent number
US08604038B2

Reaction notes

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