Benzyl chloroformate → 3-(N-Carbobenzyloxy-3-fluoroanilin-4-yl)-3-hydroxy-1-(1,1-diphenylmethyl)azetidine

HRID 1276455Notes

Reaction equation

HRID 1276455 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:25])[CH2:11][N:10]([CH:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:9]2)=[C:4]([F:26])[CH:3]=1.C(=O)(O)[O-].[Na+].Cl[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34]>CC(C)=O.O>[C:33]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:25])[CH2:9][N:10]([CH:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:11]2)=[C:4]([F:26])[CH:3]=1)([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34]

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 226257053-(4-Amino-2-fluorophenyl)-3-hydroxy-1-(1,1-diphenylmethyl)azetidine

Product 1

HCID 226256753-(N-Carbobenzyloxy-3-fluoroanilin-4-yl)-3-hydroxy-1-(1,1-diphenylmethyl)azetidine

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a solution of 3-(4-amino-2-fluorophenyl)-3-hydroxy-1-(1,1-diphenylmethyl)azetidine (Example 81, Step 1, 5.10 g, 14.7 mmol) in acetone (75 mL) was added a solution of sodium bicarbonate (2.52 g, 30.0 mmol) in water (40 mL) to give a creamy suspension. Benzyl chloroformate (2.57 g, 15.1 mmol) was added and stirring continued overnight. The suspension was filtered and the acetone evaporated. The residue was partitioned between ethyl acetate (200 mL) and water (50 mL). The organic layer was washed with brine (50 mL), dried over magnesium sulfate, filtered and evaporated to leave an amber foam. Chromatography over silica gel (150 g, 40-60 μM) eluting with 1-2% methanol-methylene chloride gave the title compound as a cream foam. HRMS: meas. 483.2087, theory 483.2084.

Workup

  1. customto give a creamy suspension
  2. filtrationThe suspension was filtered
  3. customthe acetone evaporated
  4. customThe residue was partitioned between ethyl acetate (200 mL) and water (50 mL)
  5. washThe organic layer was washed with brine (50 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto leave an amber foam
  10. washChromatography over silica gel (150 g, 40-60 μM) eluting with 1-2% methanol-methylene chloride

Sources & evidence

ORD record
ord-e77414a63ae64e289e6e7a0b2fdff898
Source dataset
uspto-grants-2000_12
Patent number
US06166056

Reaction notes

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