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

HRID 2265714Notes

Reaction equation

HRID 2265714 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 under a nitrogen atmosphere in an ice-ethanol bath. 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 min. After the dropwise addition, stirring was carried out at the same temperature for 30 min. The reaction mixture was filtered and washed with tetrahydrofuran (30 ml). The filtrate was added dropwise over 15 min to an aqueous (15 ml) solution of sodium borohydride (1.33 g) cooled in an ice water bath. Upon completion of the dropwise addition, the reaction mixture was stirred at room temperature. To the reaction mixture was gradually added 1N hydrochloric acid (35 ml) to decompose 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 provide the titled compound as a pale brown solid (1.59 g, 54%).

Workup

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

Sources & evidence

ORD record
ord-78e885fcd45a4a56955f26d6a21c1b71
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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