Trifluoroacetic acid → (3S)-4-{[(9H-Fluoren-9-yl)methoxy]carbonyl}morpholine-3-carboxylic acid

HRID 2277094Notes

Reaction equation

HRID 2277094 reaction equation
FC(F)(F)C(O)=O.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][C@H:16]1[C:21]([OH:23])=[O:22])=[O:14])([CH3:11])(C)C.C(Cl)(OCC1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]2[C:29]1=[CH:30][CH:31]=[CH:32][CH:33]=2)=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.O1CCOCC1.O>[CH:39]1[C:40]2[CH:11]([CH2:8][O:12][C:13]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][C@H:16]3[C:21]([OH:23])=[O:22])=[O:14])[C:29]3[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:35]=2[CH:36]=[CH:37][CH:38]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 343679-Fluorenylmethyl chloroformateHCID 1512537(3S)-4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acid

Product 1

HCID 1502080(3S)-4-{[(9H-Fluoren-9-yl)methoxy]carbonyl}morpholine-3-carboxylic acidYield 83.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Trifluoroacetic acid (10 mL) was added to a solution of (S)-4-(tert-butoxycarbonyl) morpholine-3-carboxylic acid (5.00 g, 21.64 mmol) in CH2Cl2 (40 mL) dropwise at 0° C. and the reaction mixture was stirred at room temperature for 5 h. The reaction mixture was concentrated to dryness and the crude residue (2.80 g, 21.30 mmol) was dissolved in a mixture of dioxane (30 mL) and water (10 mL). The suspension was cooled to 0° C., FMOC-Cl (6.60 g, 25.60 mmol) and K2CO3 (11.60 g, 84.2 mmol) were added, and the mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated, diluted with water (20 mL) and acidified with 1M aqueous HCl (30 mL) to pH 2-3. The resulting mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine solution (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the title compound (6.41 g) as colorless oil which was used in the next step without further purification.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. temperatureThe suspension was cooled to 0° C.
  3. stirringthe mixture was stirred at room temperature for 3 h
  4. concentrationThe reaction mixture was concentrated
  5. additiondiluted with water (20 mL)
  6. extractionThe resulting mixture was extracted with EtOAc (3×50 mL)
  7. washThe combined organic layers were washed with brine solution (50 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e6e0cf044f25437094253a3e1955e354
Source dataset
uspto-grants-2015_09
Patent number
US09133147B2

Reaction notes

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