Tetrahydrofuran → HCID 66955235, 화합물

HRID 1948525노트

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HRID 1948525 반응식
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12](F)=[O:13])[C:8]=2[C:15]([F:18])([F:17])[F:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.[OH:28][CH:29]([C:43]1[CH:48]=[CH:47][C:46](/[C:49](=[N:51]/O)/[NH2:50])=[CH:45][CH:44]=1)[CH2:30][N:31]1[CH2:36][CH2:35][CH2:34][C@H:33]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:32]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C(#N)C.C(OCC)(=O)C>[OH:28][CH:29]([C:43]1[CH:48]=[CH:47][C:46]([C:49]2[N:51]=[C:12]([C:9]3[C:8]([C:15]([F:18])([F:17])[F:16])=[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[O:11][N:10]=3)[O:13][N:50]=2)=[CH:45][CH:44]=1)[CH2:30][N:31]1[CH2:36][CH2:35][CH2:34][C@H:33]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:32]1

참가 물질

8

반응물 5

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 58374105HCID 58374105, 화합물HCID 87214058HCID 87214058, 화합물

생성물 1

HCID 66955235HCID 66955235, 화합물

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

5-Phenyl-4-(trifluoromethyl)isoxazole-3-carbonyl fluoride, Int-II-D (150 mg, 0.58 mmol) was dissolved in acetonitrile (10 mL) and DIEA (0.185 mL, 1.061 mmol) and ethyl 2-((3R)-1-(2-hydroxy-2-(4-((Z)—N′-hydroxycarbamimidoyl)phenyl)ethyl)piperidin-3-yl)acetate (185 mg, 0.530 mmol) were added. After one hr, TBAF in THF (0.530 mL, 0.530 mmol) was added and the reaction mixture was stirred overnight at room temperature. LCMS shows two new peaks. One is the desired mass and the other has a much higher mass which corresponds to double addition of acid fluoride. The reaction mixture was diluted with ethyl acetate and washed with saturated NaCl. The organic layer was dried with MgSO4, filtered, and concentrated. Solids were purified by a silica gel cartridge using an EtOAc/hexanes gradient to yield 72 mgs of ethyl 2-((3R)-1-(2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetate. MS (m+1)=571. HPLC Peak RT=3.39 minutes.

후처리

  1. washwashed with saturated NaCl
  2. dry with materialThe organic layer was dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customSolids were purified by a silica gel cartridge

출처 및 근거

ORD 기록
ord-fc763b1c63464962a4339133fbb7db1f
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399451B2

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