Ammonium Chloride → HCID 178494774, compound

HRID 630415Notes

Reaction equation

HRID 630415 reaction equation
[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:24][Si]([N-][Si](C)(C)C)(C)C.[Li+].[OH:34][C:35]([C:68]1[S:69][CH:70]=[CH:71][CH:72]=1)([C:63]1[S:64][CH:65]=[CH:66][CH:67]=1)[C:36]([O:38][C@H:39]1[CH2:44][CH2:43][C@H:42]([N:45]([CH2:47][CH2:48][C:49]([NH:51][C:52]2[CH:57]=[C:56]([O:58][CH3:59])[C:55](C=O)=[CH:54][C:53]=2[Cl:62])=[O:50])[CH3:46])[CH2:41][CH2:40]1)=[O:37].[Cl-].[NH4+]>>[OH:34][C:35]([C:68]1[S:69][CH:70]=[CH:71][CH:72]=1)([C:63]1[S:64][CH:65]=[CH:66][CH:67]=1)[C:36]([O:38][C@H:39]1[CH2:40][CH2:41][C@H:42]([N:45]([CH2:47][CH2:48][C:49]([NH:51][C:52]2[CH:57]=[C:56]([O:58][CH3:59])[C:55](/[CH:24]=[CH:4]/[O:3][CH3:2])=[CH:54][C:53]=2[Cl:62])=[O:50])[CH3:46])[CH2:43][CH2:44]1)=[O:37]

Participants

5

Reactant 4

HCID 25517Ammonium ChlorideHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 2733832Lithium HexamethyldisilazideHCID 178493271HCID 178493271, compound2×

Product 1

HCID 178494774HCID 178494774, compoundYield 56%

Procedure

To a suspension of (methoxymethyl) triphenylphosphonium chloride (0.83 g, 2.43 mmol) in anhydride tetrahydrofuran (4.3 mL) was added dropwise a solution of lithium bis(trimethylsilyl) amide 1M (2.43 mL, 2.43 mmol) at 0° C. under nitrogen atmosphere. The mixture was stirred for 30 minutes, then a solution of trans-4-((3-(2-chloro-4-formyl-5-methoxyphenylamino)-3-oxopropyl)(methyl)amino)cyclohexyl hydroxy(di-2-thienyl)acetate (intermediate 43; 0.41 g, 0.69 mmol) in anhydride tetrahydrofuran (2.1 mL) was added dropwise into the mixture. The reaction was stirred for 30 minutes at 0° C. and for 1.5 hours at room temperature. The crude was added into a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed with water, brine, dried and the solvent was removed under reduced pressure giving an orange solid. This crude was purified by column chromatography with silica gel, eluting with methylene chloride/isopropanol (93:7) to give the title compound as a white solid (56%).

Workup

  1. stirringThe reaction was stirred for 30 minutes at 0° C. and for 1.5 hours at room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water, brine
  4. customdried
  5. customthe solvent was removed under reduced pressure
  6. customgiving an orange solid
  7. customThis crude was purified by column chromatography with silica gel
  8. washeluting with methylene chloride/isopropanol (93:7)

Sources & evidence

ORD record
ord-8e5d6d726f224662837bf3d034b8cdb1
Source dataset
uspto-grants-2016_04
Patent number
US09315463B2

Reaction notes

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