Triphenylphosphine → (2S,4S)-1-tert-butyl 2-methyl 4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)pyrrolidine-1,2-dicarboxylate

HRID 1877315Notes

Reaction equation

HRID 1877315 reaction equation
[CH3:1][O:2][C:3]1[C:12]([CH3:13])=[C:11]2[C:6]([C:7]([OH:23])=[CH:8][C:9]([C:14]3[S:15][CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[N:18]=3)=[N:10]2)=[CH:5][CH:4]=1.[CH3:24][O:25][C:26](=[O:40])[C@@H:27]1[CH2:31][C@@H:30](O)[CH2:29][N:28]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[CH3:1][O:2][C:3]1[C:12]([CH3:13])=[C:11]2[C:6]([C:7]([O:23][C@@H:30]3[CH2:29][N:28]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@H:27]([C:26]([O:25][CH3:24])=[O:40])[CH2:31]3)=[CH:8][C:9]([C:14]3[S:15][CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[N:18]=3)=[N:10]2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 5363146Diisopropyl azodicarboxylate2×HCID 178487696HCID 178487696, compound

Product 1

HCID 66650411(2S,4S)-1-tert-butyl 2-methyl 4-(7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-yloxy)pyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The 7-methoxy-8-methyl-2-(4-(trifluoromethyl)thiazol-2-yl)quinolin-4-ol BO (10.0 g, 1 eq.), the N-Boc-trans-4-hydroxyproline methyl ester BP (7.20 g, 1 eq.), and the triphenylphosphine (11.56 g, 1.5 eq.) in suspension in THF (250 mL) under N2 were cooled down to 0° C. The DIAD (8.70 mL, 1.5 eq.) was added dropwise. The reaction mixture was allowed to warm up and stir at room temperature for 1.25 hrs, then cooled again at 0° C. and additional 1 more eq. of DIAD was added. The reaction mixture was stirred for 2 hrs at room temperature, and then concentrated in vacuo to 50 mL. Water and ethyl acetate were added and the phases were separated. The aqueous layer was further extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel to yield compound BQ (16.75 g, 87% purity). MS (ESI, EI+) m/z=568.3 (MH+); 626.5 (M+OAc−).

Workup

  1. temperatureto warm up
  2. temperaturecooled again at 0° C.
  3. stirringThe reaction mixture was stirred for 2 hrs at room temperature
  4. concentrationconcentrated in vacuo to 50 mL
  5. additionWater and ethyl acetate were added
  6. customthe phases were separated
  7. extractionThe aqueous layer was further extracted with ethyl acetate
  8. washThe organic layer was washed with brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by chromatography on silica gel
  12. customto yield compound BQ (16.75 g, 87% purity)

Sources & evidence

ORD record
ord-26948e8699cb462a90b0424e97a7497b
Source dataset
uspto-grants-2012_11
Patent number
US08309737B2

Reaction notes

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