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Triphenylphosphine → Methyl 2-{3-[2-(trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboxylate

HRID 2355058
Notes
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Reaction equation

HRID 2355058 reaction equation
[OH:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[S:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][N:11]=2)[CH2:3]1.[F:16][C:17]([F:26])([F:25])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[F:16][C:17]([F:26])([F:25])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[O:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[S:8][C:9]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][N:11]=2)[CH2:3]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 679582-TrifluoromethylphenolHCID 5462977Diethyl azodicarboxylateHCID 68452743Methyl 2-(3-hydroxypyrrolidin-1-yl)-1,3-thiazole-5-carboxylate

Product 1

HCID 68452698Methyl 2-{3-[2-(trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-(3-hydroxypyrrolidin-1-yl)-1,3-thiazole-5-carboxylate (1 g, 4.4 mmol), 2-(trifluoromethyl)phenol (0.8 g, 4.9 mmol) and triphenylphosphine (1.5 g, 5.7 mmol) in THF at rt was added DEAD (900 μL, 5.7 mmol) over 5-10 min. The mixture was stirred at rt for 2 days. Solvent was evaporated. The residue was diluted with EtOAc and washed successively with 1 N aqueous NaOH and brine. The EtOAc layer was separated, dried (Na2SO4) and concentrated. CombiFlash chromatography (40 g, 30-70% EtOAc in hexanes in 20 min, 35 mL/min, 18 mL/fraction) gave a semi-solid which was triturated with hexanes-diethyl ether to give a white solid which was filtered off. Crystals appeared in the mother liquor after standing. These crystals were collected to give the title compound, contaminated with about 5-10% impurity. 1H NMR (400 MHz, acetone-d6): δ 7.84 (s, 1 H), 7.67 (m, 2 H), 7.41 (d, 1 H), 7.17 (t, 1H), 5.51 (s, 1H), 3.95 (m, 1H), 3.80-3.65 (m, 6H), 2.60-2.46 (m, 2H).

Workup

  1. customSolvent was evaporated
  2. additionThe residue was diluted with EtOAc
  3. washwashed successively with 1 N aqueous NaOH and brine
  4. customThe EtOAc layer was separated
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customCombiFlash chromatography (40 g, 30-70% EtOAc in hexanes in 20 min, 35 mL/min, 18 mL/fraction) gave a semi-solid which
  8. customwas triturated with hexanes-diethyl ether
  9. customto give a white solid which
  10. filtrationwas filtered off
  11. customThese crystals were collected

Sources & evidence

ORD record
ord-17f3f2f32f6e4698983e1042e6197352
Source dataset
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07754745B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes