Hydrochloric Acid → 3-hydroxy-2-hydroxymethyl-2-[4-(9-hydroxy-2-methyl-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-propionic acid

HRID 541160Notes

Reaction equation

HRID 541160 reaction equation
[OH:1][C:2]1([C:29]([F:32])(F)[F:30])[C:14]2[CH:13]=[C:12]([CH3:15])[CH:11]=[C:10]([C:16]3[CH:17]=[N:18][N:19]([CH2:21][C:22]([O:24]C(C)(C)C)=[O:23])[CH:20]=3)[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[CH2:33]=[O:34].[F-:35].C([N+](CCCC)(CCCC)CCCC)CCC.Cl.CN(C)[CH:56]=[O:57]>O1CCCC1.O>[OH:34][CH2:33][C:21]([CH2:56][OH:57])([N:19]1[CH:20]=[C:16]([C:10]2[C:9]3[C:8]4[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=4)[C:2]([OH:1])([C:29]([F:32])([F:30])[F:35])[C:14]=3[CH:13]=[C:12]([CH3:15])[CH:11]=2)[CH:17]=[N:18]1)[C:22]([OH:24])=[O:23]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 6228DimethylformamideHCID 2724141Tetrabutylammonium FluorideHCID 59492691t-butyl[4-(9-hydroxy-2-methyl-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-acetate

Product 1

HCID 594926873-hydroxy-2-hydroxymethyl-2-[4-(9-hydroxy-2-methyl-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-propionic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of an optically active form (17.8 g) of t-butyl [4-(9-hydroxy-2-methyl-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-acetate and paraformaldehyde (12.0 g) in dimethylformamide (60 ml) was added at room temperature a 1M solution (120 ml) of tetrabutylammonium fluoride in tetrahydrofuran, and the mixture was stirred at 95° C. for 3 hr. To the reaction mixture were added 1N hydrochloric acid (180 ml) and water (90 ml), and the mixture was extracted with ethyl acetate (180 ml). The separated aqueous layer was extracted twice with ethyl acetate (90 ml). The combined organic layer was successively washed once with 1N hydrochloric acid (90 ml), twice with water (90 ml) and once with saturated brine (90 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (15.5 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (180 ml)
  2. extractionThe separated aqueous layer was extracted twice with ethyl acetate (90 ml)
  3. washThe combined organic layer was successively washed once with 1N hydrochloric acid (90 ml), twice with water (90 ml) and once with saturated brine (90 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e1f7fa1f22ab4fe98466d2466353ce92
Source dataset
uspto-grants-2014_10
Patent number
US08871934B2

Reaction notes

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