1,2-Dichloroethane → 4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid methyl ester

HRID 900554Notes

Reaction equation

HRID 900554 reaction equation
[CH3:1]CN(C(C)C)C(C)C.I[C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[CH:13][CH:12]=1.C1C=NC2N(O)N=NC=2C=1.[CH2:30]([Cl:33])[CH2:31]Cl.O[C@@H]1CC[N:37]([C:40]([C:42]2[CH:47]=[CH:46][C:45](OC(F)(F)F)=[CH:44][CH:43]=2)=O)[C@H]1C(NOCC1C=CC=CC=1)=O>CN(C=O)C.CCOC(C)=O.CCCCCC>[CH3:1][O:17][C:15](=[O:16])[C:14]1[CH:18]=[CH:19][C:11]([C:46]#[C:45][C:44]#[C:43][C:42]2[CH:40]=[N:37][C:30]([Cl:33])=[CH:31][CH:47]=2)=[CH:12][CH:13]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 120854-Iodobenzoic acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 59697601((2r,3r)-3-Hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl)-n-(phenylmethoxy)carboxamide

Product 1

HCID 865950674-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid methyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

DIEA (9.7 ml, 55.1 mmol) was added to a stirred solution of 4-iodo-benzoic acid (5.49 g, 22.2 mmol), HOAT (3.08 g, 22.6 mmol), EDC (4.33 g, 22.6 mmol) in DMF (85 ml). After 2 min., the H-DAP(Boc)-OMe (1) was added in one portion. After 12 hours, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (1:1) (500 ml). The organic phase was washed with 1N HCl (2×80 ml), 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (1:1). The fractions with product were evaporated to give 9.3 g of product (3-tert-Butoxycarbonylamino-2-(4-iodo-benzoylamino)-propionic acid methyl ester) in 93% yield. This product was converted to analogues in a similar manner as the aforementioned Examples.

Workup

  1. waitAfter 12 hours
  2. washThe organic phase was washed with 1N HCl (2×80 ml), 1N NaOH (2×80 ml), water (2×80 ml), sat. brine (80 ml)
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give crude product
  7. filtrationThe residue was filtered through a filter plug of silica eluting with EtOAc/hexane (1:1)
  8. customThe fractions with product were evaporated

Sources & evidence

ORD record
ord-39cfc21ca00e41b8b4fff50fc3e9098a
Source dataset
uspto-grants-2008_04
Patent number
US07358359B2

Reaction notes

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