1,2-Dichloroethane → HCID 70170745, 화합물

HRID 2306207노트

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HRID 2306207 반응식
[C:1]1([C:7]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:8]2[CH:12]=[C:11]([CH2:13][C:14]([O-:16])=O)[N:10]=[CH:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].Cl.[NH2:31][C@H:32]1[CH2:36][CH2:35][N:34]([C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[C:44]([O:47][Si](C(C)(C)C)(C)C)[CH:45]=3)[CH:40]=[CH:39][CH:38]=2)[C:33]1=[O:55].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)C(C)C)(C)C>CN(C=O)C>[OH:47][C:44]1[CH:45]=[C:46]2[C:41]([CH:40]=[CH:39][CH:38]=[C:37]2[N:34]2[CH2:35][CH2:36][C@H:32]([NH:31][C:14](=[O:16])[CH2:13][C:11]3[N:10]=[CH:9][N:8]([C:7]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:12]=3)[C:33]2=[O:55])=[CH:42][CH:43]=1

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 23690736HCID 23690736, 화합물HCID 70170739HCID 70170739, 화합물

생성물 1

HCID 70170745HCID 70170745, 화합물

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mixture of lithium [1-(triphenylmethyl)-1H-imidazol-4-yl]acetate, as described above in Step B, (4.40 g, 11.6 mmol), (S)-3-amino-1-[7-(tert-butyldimethylsilyloxy)naphthalen-1-yl]-2-oxopyrrolidine hydrochloride, as described above in Step A (3.86 g, 9.84 mmol), HOBT (1.60 g, 11.8 mmol), EDC (2.30 g, 12.0 mmol), and N,N-diisopropylethylamine (6.00 mL, 34.4 mmol) was stirred in DMF (80 mL) at ambient temperature for 18 hours. The solvent was removed under reduced pressure and the residue was partitioned between saturated aqueous NaHCO3 (50 mL) and CHCl3 (75 mL). The aqueous layer was extracted further with CHCl3 (2×50 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was dissolved in dry THF (75 mL) and TBAF (5 mL of a 1.0 M solution in TBF, 5 mmol) was added. The resulting mixture was stirred at ambient temperature for 30 min, then quenched with saturated aqueous NH4Cl (30 mL) and most of the TBF was removed under reduced pressure. The residual mixture was poured into saturated aqueous NaHCO3 (50 mL) and CH2Cl2 (100 mL). The aqueous layer was extracted further with CH2Cl2 (2×50 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica, eluting with a gradient of CH2Cl2—2% to 4% MeOH to yield the titled product.

후처리

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was partitioned between saturated aqueous NaHCO3 (50 mL) and CHCl3 (75 mL)
  3. extractionThe aqueous layer was extracted further with CHCl3 (2×50 mL)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude product was dissolved in dry THF (75 mL)
  8. additionTBAF (5 mL of a 1.0 M solution in TBF, 5 mmol) was added
  9. customquenched with saturated aqueous NH4Cl (30 mL) and most of the TBF
  10. customwas removed under reduced pressure
  11. additionThe residual mixture was poured into saturated aqueous NaHCO3 (50 mL) and CH2Cl2 (100 mL)
  12. extractionThe aqueous layer was extracted further with CH2Cl2 (2×50 mL)
  13. dry with materialThe combined organic extracts were dried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe residue was purified by flash column chromatography on silica
  17. washeluting with a gradient of CH2Cl2—2% to 4% MeOH

출처 및 근거

ORD 기록
ord-a0cd53b79914443589e00383245ae180
출처 데이터셋
uspto-grants-2002_08
특허 번호
US06441017B1

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