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 448844노트

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HRID 448844 반응식
[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

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 5363146Diisopropyl azodicarboxylate2회HCID 178487696HCID 178487696, 화합물

생성물 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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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−).

후처리

  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)

출처 및 근거

ORD 기록
ord-acfd0bc7e59c4c6f90c1e8ab2ce4b8cd
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481748B2

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