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Potassium Phosphate, Tribasic → Methyl 2-((S)-6-((R)-4-(4-cyano-2,6-dimethylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

HRID 237513
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HRID 237513 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5](B2OC(C)(C)C(C)(C)O2)=[C:6]2[C:10]=1[C@H:9]([O:11][C:12]1[CH:25]=[CH:24][C:15]3[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=3[CH:13]=1)[CH2:8][CH2:7]2.Br[C:36]1[C:43]([CH3:44])=[CH:42][C:39]([C:40]#[N:41])=[CH:38][C:37]=1[CH3:45].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:40]([C:39]1[CH:42]=[C:43]([CH3:44])[C:36]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[C:10]3[C:6]=2[CH2:7][CH2:8][C@H:9]3[O:11][C:12]2[CH:25]=[CH:24][C:15]3[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=3[CH:13]=2)=[C:37]([CH3:45])[CH:38]=1)#[N:41]
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참가 물질

7

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 110850704-Bromo-3,5-dimethyl-benzonitrileHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86697106{(S)-6-[(R)-7-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

생성물 1

HCID 86697175
Methyl 2-((S)-6-((R)-4-(4-cyano-2,6-dimethylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

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온도
100 °C

실험 절차

In a microwave vial, methyl 2-((S)-6-((R)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate (200 mg), 4-bromo-3,5-dimethylbenzonitrile (90 mg), K3PO4 (273 mg), Palladium-(II)-acetate (10 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (17 mg) are suspended in toluene (10 mL) and water (2 mL) and purged for 10 minutes with argon. The vial is sealed and the mixture is stirred at 100° C. for 4 hours. After cooling to ambient temperature the mixture is partitioned between ethyl acetate and water. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10) to give the title compound. Yield: 85 mg; LC (method 19): tR=1.52 min; Mass spectrum (ESI+): m/z=471 [M+−H]+.

후처리

  1. customwater (2 mL) and purged for 10 minutes with argon
  2. customThe vial is sealed
  3. temperatureAfter cooling to ambient temperature the mixture
  4. customis partitioned between ethyl acetate and water
  5. dry with materialThe organic phase is dried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10)

출처 및 근거

ORD 기록
ord-924fd9d881824010af812007a8d70a13
출처 데이터셋
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08642585B2

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