Trifluoroacetic acid → 4-{[(2S)-2-Hydroxy-3-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]-oxy}benzonitrile

HRID 1351135Notes

Reaction equation

HRID 1351135 reaction equation
[C:1]([C:3]1[CH:29]=[CH:28][C:6]([O:7][CH2:8][C@@H:9]([OH:27])[CH2:10][N:11]2[CH2:18][CH:17]3[O:19][CH:13]([CH2:14][N:15](C(OC(C)(C)C)=O)[CH2:16]3)[CH2:12]2)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O>ClCCl>[OH:27][C@@H:9]([CH2:10][N:11]1[CH2:18][CH:17]2[O:19][CH:13]([CH2:14][NH:15][CH2:16]2)[CH2:12]1)[CH2:8][O:7][C:6]1[CH:28]=[CH:29][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 21076121tert-Butyl 7-[(2S)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate

Product 1

HCID 684578084-{[(2S)-2-Hydroxy-3-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)propyl]-oxy}benzonitrileYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 3 L, three-necked flask equipped with a magnetic stirrer, a thermometer and an addition funnel was charged with unpurified tert-butyl 7-[(2S)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate (100 g, from step (ii) above) and dichloromethane (1.15 L). Trifluoroacetic acid (0.352 L) was added slowly at room temperature and the resulting solution was stirred for three hours, at which point TLC analysis showed complete reaction. The contents were transferred to a single-necked flask and concentrated under vacuum. The residue was dissolved in dichloromethane (1.2 L) and washed with saturated sodium bicarbonate. The aqueous layer was separated and extracted with dichloromethane (2×0.2 L). The combined organic layers were washed with brine (0.25 L), dried over magnesium sulfate and concentrated under vacuum to afford 73 g (>100% yield) of sub-title compound as an off-white solid. The unpurified material was used in the next step.

Workup

  1. customA 3 L, three-necked flask equipped with a magnetic stirrer
  2. customreaction
  3. customThe contents were transferred to a single-necked flask
  4. concentrationconcentrated under vacuum
  5. dissolutionThe residue was dissolved in dichloromethane (1.2 L)
  6. washwashed with saturated sodium bicarbonate
  7. customThe aqueous layer was separated
  8. extractionextracted with dichloromethane (2×0.2 L)
  9. washThe combined organic layers were washed with brine (0.25 L)
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-18a695895e72443e98b2850a3fdef8a5
Source dataset
uspto-grants-2007_05
Patent number
US07217708B2

Reaction notes

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