Iodine → (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(2-(4-(heptyloxy)phenyl)thiazol-4-yl)phenyl)propanoate

HRID 716403ノート

反応式

HRID 716403 の反応式
II.[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16]I)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]=[C:27]([C:30]3[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=3)[S:28][CH:29]=2)=[CH:21][CH:20]=1.C(Cl)Cl>CN(C=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[N:26]=[C:27]([C:30]3[CH:31]=[CH:32][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:34][CH:35]=3)[S:28][CH:29]=2)=[CH:23][CH:24]=1)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4]

参加物

9

反応物 4

HCID 807Iodine2 回HCID 6344DichloromethaneHCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 86689666HCID 86689666、化合物

生成物 1

HCID 86689667(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(2-(4-(heptyloxy)phenyl)thiazol-4-yl)phenyl)propanoate収率 84%

試薬・触媒・溶媒 4

HCID 23994Zinc触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl触媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
50 °C

実験手順

To a stirring mixture of zinc (182 mg, 2.79 mmol) in DMF (2 mL) was added diiodine (35.4 mg, 0.14 mmol). When the color was discharged, further diiodine (35.4 mg, 0.14 mmol) and (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (306 mg, 0.93 mmol) were added. After 30 min, DMF (1 mL) was added and the mixture de-gassed by bubbling through N2. To the reaction mixture were added 4-(4-bromophenyl)-2-(4-(heptyloxy)phenyl)thiazole (400 mg, 0.93 mmol), Pd2dba3 (21 mg, 0.02 mmol) and dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (19 mg, 0.05 mmol), the mixture was further de-gassed then heated to 50° C. for 3 h. The reaction mixture was cooled and purified by column chromatography (10-80% EA in iso-hexanes). The product obtained was taken into DCM (4 mL) and washed with water (20 mL) and dried through a hydrophobic frit. The organics were suspended in ACN (4 mL) and concentrated to afford 432 mg (83%) of (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(2-(4-(heptyloxy)phenyl)thiazol-4-yl)phenyl)propanoate as a yellow foam. LCMS-ESI (m/z) calculated for C31H40N2O5S: 552.7; no ion observed, tR=3.36 min. (Method 4).

後処理

  1. customthe mixture de-gassed
  2. customby bubbling through N2
  3. customthe mixture was further de-gassed
  4. temperatureThe reaction mixture was cooled
  5. custompurified by column chromatography (10-80% EA in iso-hexanes)
  6. customThe product obtained
  7. washwashed with water (20 mL)
  8. customdried through a hydrophobic frit
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-d1b17b6a2c55445e98c70695e5f8280f
出典データセット
uspto-grants-2015_11
特許番号
US09187522B2

反応ノート

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