Water → tert-Butyl ((3R,4R,5S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate

HRID 1499501Notes

Reaction equation

HRID 1499501 reaction equation
[Si:1]([O:8][C@@H:9]1[C@@H:14]([CH3:15])[CH2:13][N:12]([C:16]2[C:21]([N+:22]([O-])=O)=[CH:20][N:19]=[C:18]3[O:25][CH2:26][CH2:27][C:17]=23)[CH2:11][C@H:10]1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl-].[NH4+].O>[Fe].CCO>[NH2:22][C:21]1[C:16]([N:12]2[CH2:13][C@H:14]([CH3:15])[C@@H:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3])[C@H:10]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:11]2)=[C:17]2[CH2:27][CH2:26][O:25][C:18]2=[N:19][CH:20]=1

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 86726731tert-Butyl [(3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-1-(5-nitro-2,3-dihydrofuro[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate

Product 1

HCID 86726732tert-Butyl ((3R,4R,5S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamateYield 98.4%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of tert-butyl [(3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-1-(5-nitro-2,3-dihydrofuro[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate (73.4 mg, 0.144 mmol), iron powder (89.0 mg, 1.59 mmol), and ammonium chloride (151.4 mg, 2.830 mmol) was added EtOH (2.0 mL) followed by water (0.50 mL, 28 mmol). The mixture was stirred at 80° C. for 1 h. The reaction mixture was filtered through a pad of diatomaceous earth. The diatomaceous earth pad was eluted with a 10% aqueous solution of K3PO4 (20 mL), and EtOAc (20 mL). The organic layers were washed with brine (20 mL), dried over Na2SO4, and concentrated to give the crude sub-title compound (67.8 mg). The crude product was used directly in the next step without further purification. LCMS calc. for C24H43N4O4Si (M+H)+: m/z=479.3. found 479.3.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of diatomaceous earth
  2. washThe diatomaceous earth pad was eluted with a 10% aqueous solution of K3PO4 (20 mL), and EtOAc (20 mL)
  3. washThe organic layers were washed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-9ba2b8e499064a1db1d5c947c3aa09b3
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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