Water → HCID 58043125, compound

HRID 1035192Notes

Reaction equation

HRID 1035192 reaction equation
[H-].[Na+].[CH3:3][N:4]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:8]=1[F:14])[CH3:5].CS(O[CH:20]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21]1)(=O)=O.O>CN(C=O)C>[CH3:5][N:4]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH:20]2[CH2:21][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23]2)=[CH:9][C:8]=1[F:14])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 10753243Tert-butyl 3-(methanesulfonyloxy)azetidine-1-carboxylateHCID 58043093HCID 58043093, compound

Product 1

HCID 58043125HCID 58043125, compoundYield 62.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
80 °C

Procedure

A mixture of NaH (55-65% disp. in oil, 0.31 g, 7.7 mmol) in dry DMF (10 mL) under nitrogen was cooled by an ice-bath. A solution of 26A (1.0 g, 5.9 mmol) in DMF (10 mL) was added drop-wise over 10 minutes. The mixture was stirred for 30 minutes and then tert-butyl 3-[(methylsulfonyl)oxy]azetidine-1-carboxylate (1.63 g, 6.5 mmol) in DMF (10 mL) was added. The mixture was heated to 80° C. over night and then cooled to RT. Water (100 mL) was added and the mixture was extracted three times with EtOAc (50 mL). The combined organic phases were filtered through a phase separator and the solvent was removed by evaporation. The residue was purified by preparative chromatography on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 10-50% acetonitrile in water/acetonitrile/formic acid (95/5/0.2), 100 mL/min. Fractions were collected, pooled and concentrated in vacuo. DCM was added and the solution was filtered through a phase separator and concentrated by evaporation. There was obtained 1.2 g (55%) of 26B as a solid. 1H NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 2.58 (s, 6H), 3.90 (s, 2H), 3.95-4.05 (m, 2H), 4.25-4.35 (m, 2H), 4.81-4.92 (m, 1H), 6.45-6.65 (m, 2H), 7.35-7.45 (m, 1H), 8.42 (s, 1H).

Workup

  1. temperaturewas cooled by an ice-bath
  2. temperaturecooled to RT
  3. extractionthe mixture was extracted three times with EtOAc (50 mL)
  4. filtrationThe combined organic phases were filtered through a phase separator
  5. customthe solvent was removed by evaporation
  6. customThe residue was purified by preparative chromatography on a Kromasil C8 column (10 μm 250×20 ID mm)
  7. customFractions were collected
  8. concentrationconcentrated in vacuo
  9. additionDCM was added
  10. filtrationthe solution was filtered through a phase separator
  11. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-f5ff08612ab44924a69a431772c8c57e
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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