Tetrahydrofuran → tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-{3-[({6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate

HRID 1499596Notes

Reaction equation

HRID 1499596 reaction equation
C([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH:37][C:38]([C:40]3[CH:45]=[CH:44][C:43]([F:46])=[C:42]([C:47]4[C:52]([F:53])=[CH:51][C:50]([CH2:54][O:55][CH3:56])=[CH:49][C:48]=4[F:57])[N:41]=3)=[O:39])[C:13]([N:14]3[CH2:19][C@H:18]([CH3:20])[C@@H:17]([O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[C@H:16]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=O)C.C1COCC1.[OH-].[Na+]>CO>[Si:22]([O:21][C@@H:17]1[C@@H:18]([CH3:20])[CH2:19][N:14]([C:13]2[C:12]([NH:37][C:38]([C:40]3[CH:45]=[CH:44][C:43]([F:46])=[C:42]([C:47]4[C:52]([F:53])=[CH:51][C:50]([CH2:54][O:55][CH3:56])=[CH:49][C:48]=4[F:57])[N:41]=3)=[O:39])=[CH:11][N:10]=[C:9]3[CH:5]([OH:4])[CH2:6][CH2:7][C:8]=23)[CH2:15][C@H:16]1[NH:29][C:30](=[O:31])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])([C:25]([CH3:28])([CH3:26])[CH3:27])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 867268104-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)-3-[({6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

Product 1

HCID 86726812tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-{3-[({6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the amide intermediate prepared as described above THF (5 mL), MeOH (5 mL) and 1.0 M aq. NaOH (5 mL, 5 mmol) were added. The mixture was stirred at room temperature for 20 min. The volatile organic solvents were removed under reduced pressure. The residue was extracted with EtOAc (2 times). The combined organic phases were then washed with brine, dried over Na2SO4, and concentrated under reduced pressure to give an alcohol intermediate, tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-{3-[({6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate.

Workup

  1. additionwere added
  2. customThe volatile organic solvents were removed under reduced pressure
  3. extractionThe residue was extracted with EtOAc (2 times)
  4. washThe combined organic phases were then washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0555140dae924e57af0c9eade9cf274b
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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