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

HRID 237437

반응식

HRID 237437 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:48]([CH3:49])=[CH:47][C:39]([O:40][CH2:41][C:42]2([CH3:46])[CH2:45][O:44][CH2:43]2)=[CH:38][C:37]=1[CH3:50].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1>[CH3:50][C:37]1[CH:38]=[C:39]([O:40][CH2:41][C:42]2([CH3:46])[CH2:45][O:44][CH2:43]2)[CH:47]=[C:48]([CH3:49])[C:36]=1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[C:10]2[C:6]=1[CH2:7][CH2:8][C@H:9]2[O:11][C:12]1[CH:25]=[CH:24][C:15]2[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=2[CH:13]=1

참가 물질

5

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 866971023-((4-Bromo-3,5-dimethylphenoxy)methyl)-3-methyloxetaneHCID 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 86697105Methyl 2-((S)-6-((R)-4-(2,6-dimethyl-4-((3-methyloxetan-3-yl)methoxy)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

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 (500 mg), 3-((4-bromo-3,5-dimethylphenoxy)methyl)-3-methyloxetane (450 mg), K3PO4 (450 mg) are suspended in toluene (2.5 mL) and water (250 μL) and purged for 10 minutes with argon. Palladium-(II)-acetate (12 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (44 mg) are added, the vial is sealed and the mixture is stirred at 100° C. for 4 hours. After cooling to room temperature the mixture is partitioned between diethylether and saturated aqueous NH4Cl solution. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10→60:40) to give the title compound. Yield: 420 mg; LC (method 4): tR=1.93 min; Mass spectrum (ESI+): m/z=569 [M+Na]+.

후처리

  1. customwater (250 μL) and purged for 10 minutes with argon
  2. additionPalladium-(II)-acetate (12 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (44 mg) are added
  3. customthe vial is sealed
  4. temperatureAfter cooling to room temperature the mixture
  5. customis partitioned between diethylether and saturated aqueous NH4Cl solution
  6. dry with materialThe organic phase is dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10→60:40)

출처 및 근거

ORD 기록
ord-45cddba526a648ec8e3490433c700826
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642585B2

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