Triethylamine → (1-Benzhydrylazetidin-3-yl)methanol

HRID 1712655Notes

Reaction equation

HRID 1712655 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([C:18](O)=[O:19])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C(Cl)(=O)OCC>O1CCCC1>[CH:1]([N:14]1[CH2:17][CH:16]([CH2:18][OH:19])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 27354401-(Diphenylmethyl)azetidine-3-carboxylic acid

Product 1

HCID 2758715(1-Benzhydrylazetidin-3-yl)methanolYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-Benzhydryl-3-azetidinecarboxylic acid (3.12 g) was suspended in tetrahydrofuran (60 ml), and cooled in an ice-methanol bath under a nitrogen atmosphere. Triethylamine (1.96 ml) was added dropwise, and a solution of ethyl chlorocarbonate (1.34 ml) in tetrahydrofuran (5 ml) was added dropwise over 20 minutes. After the addition, the reaction mixture was stirred at the same temperature for 30 minutes. The reaction mixture was filtered, and the residue was washed with tetrahydrofuran (30 ml). The filtrate was added dropwise to a solution of an aqueous (15 ml) solution of sodium borohydride (1.33 g) cooled in an ice water bath over 15 minutes. After the addition, the reaction mixture was stirred at room temperature. 1N hydrochloric acid (35 ml) was gradually added to the reaction mixture to degrade excess sodium borohydride, and a 1N aqueous solution of sodium hydroxide (35 ml) was added. This was extracted with ethyl acetate (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the residue was dried under reduced pressure to give the title compound (1.59 g, 54%) as a pale brown solid.

Workup

  1. temperaturecooled in an ice-methanol bath under a nitrogen atmosphere
  2. additionAfter the addition
  3. filtrationThe reaction mixture was filtered
  4. washthe residue was washed with tetrahydrofuran (30 ml)
  5. additionThe filtrate was added dropwise to a solution of an aqueous (15 ml) solution of sodium borohydride (1.33 g)
  6. temperaturecooled in an ice water bath over 15 minutes
  7. additionAfter the addition
  8. stirringthe reaction mixture was stirred at room temperature
  9. addition1N hydrochloric acid (35 ml) was gradually added to the reaction mixture
  10. additiona 1N aqueous solution of sodium hydroxide (35 ml) was added
  11. extractionThis was extracted with ethyl acetate (100 ml)
  12. washThe organic layer was washed with brine
  13. dry with materialdried over anhydrous sodium sulfate
  14. concentrationThe solvent was concentrated
  15. customthe residue was dried under reduced pressure

Sources & evidence

ORD record
ord-5e8b1b2e93a34395b9a2ba1bb0bbf4b0
Source dataset
uspto-grants-2010_09
Patent number
US07790885B2

Reaction notes

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