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

HRID 237520ノート

反応式

HRID 237520 の反応式
[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.I[C:36]1[C:45]([CH3:46])=[CH:44][C:39]([C:40]([NH:42][CH3:43])=[O:41])=[CH:38][C:37]=1[CH3:47].[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>[CH3:47][C:37]1[CH:38]=[C:39]([C:40](=[O:41])[NH:42][CH3:43])[CH:44]=[C:45]([CH3:46])[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

参加物

6

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 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 esterHCID 866971824-iodo-N,3,5-trimethylbenzamide

生成物 1

HCID 86697181Methyl 2-((S)-6-((R)-4-(2,6-dimethyl-4-(methylcarbamoyl)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
120 °C

実験手順

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 (75 mg), 4-iodo-N,3,5-trimethylbenzamide (93 mg), K3PO4 (102 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (7 mg) are suspended in toluene (1.8 mL) and water (0.2 mL) and purged for 10 minutes with argon. Palladium-(II)-acetate (4 mg) is added, the vial is sealed and the mixture is stirred at 120° C. for 5 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 100:0→80:20) to give the title compound. Yield: 16 mg; LC (method 25): tR=1.32 min; Mass spectrum (ESI+): m/z=504 [M+H]+.

後処理

  1. customwater (0.2 mL) and purged for 10 minutes with argon
  2. additionPalladium-(II)-acetate (4 mg) is added
  3. customthe vial is sealed
  4. temperatureAfter cooling to ambient temperature the mixture
  5. customis partitioned between ethyl acetate and water
  6. dry with materialThe organic phase is dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0→80:20)

出典と根拠

ORDレコード
ord-5d16a52398ea40e19aec555ce5a203e1
出典データセット
uspto-grants-2014_02
特許番号
US08642585B2

反応ノート

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