Triethylamine → HCID 23075285, compound

HRID 2076434Notes

Reaction equation

HRID 2076434 reaction equation
[F:1][C:2]([F:20])([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([CH3:17])([CH3:16])[CH2:11][CH2:10][C:9]2([CH3:19])[CH3:18])[C:3]([OH:5])=O.[CH3:21][O:22][C:23](=[O:31])[C:24]1[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=1.CCN(CC)CC.[NH4+].[Cl-]>O=S(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:20][C:2]([F:1])([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([CH3:16])([CH3:17])[CH2:11][CH2:10][C:9]2([CH3:19])[CH3:18])[C:3]([NH:30][C:27]1[CH:26]=[CH:25][C:24]([C:23]([O:22][CH3:21])=[O:31])=[CH:29][CH:28]=1)=[O:5]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 12082Methyl 4-aminobenzoateHCID 25517Ammonium ChlorideHCID 23075286HCID 23075286, compound

Product 1

HCID 23075285HCID 23075285, compoundYield 65%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

2,2-Difluoro-2-(1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalen-6-yl)acetic acid 16 (0.70 g, 2.48 mmol) was dissolved in SOCl2 and two drops of DMF were added at 0° C. This mixture was stirred at 0° C. for 30 min and evaporated in vacuo. The resulting acid chloride was dissolved in CH2Cl2 (5 mL). Methyl-4-aminobenzoate (0.38 g, 2.48 mmol) and DMAP (30 mg, 0.25 mmol) were dissolved in CH2Cl2 (5 mL) and Et3N (2.9 mL) was added at 0° C. The solution of the acid chloride in CH2Cl2 was added and this mixture stirred for 10 min at 0° C. and then abandoned to RT for 1 h. A solution of aqueous NH4Cl 5% was added (200 mL) and the mixture was extracted with EtOAc (3×100 mL). The organic layer was washed with aqueous NaHCO3 5% (2×20 mL), brine (2×20 mL), dried over MgSO4, filtered and evaporated in vacuo. The crude product was purified by chromatography on silica using as eluent cyclohexane:EtOAc=9:1. After evaporation, methyl 4-(2,2-difluoro-2-(1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalen-6-yl)acetamido)benzoate 17 (0.67 g, 65% yield) was obtained as a beige solid.

Workup

  1. customevaporated in vacuo
  2. dissolutionThe resulting acid chloride was dissolved in CH2Cl2 (5 mL)
  3. stirringthis mixture stirred for 10 min at 0° C.
  4. waitabandoned to RT for 1 h
  5. extractionthe mixture was extracted with EtOAc (3×100 mL)
  6. washThe organic layer was washed with aqueous NaHCO3 5% (2×20 mL), brine (2×20 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe crude product was purified by chromatography on silica using as eluent cyclohexane
  11. customAfter evaporation

Sources & evidence

ORD record
ord-0fd0dad4e0354bd18bad2db5470777e4
Source dataset
uspto-grants-2011_04
Patent number
US07923579B2

Reaction notes

Loading…