1,2-Dichloroethane → HCID 70170745, compound

HRID 2306207Notes

Reaction equation

HRID 2306207 reaction equation
[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

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 23690736HCID 23690736, compoundHCID 70170739HCID 70170739, compound

Product 1

HCID 70170745HCID 70170745, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-a0cd53b79914443589e00383245ae180
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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