Triethylamine → HCID 23075289, compound

HRID 2076437Notes

Reaction equation

HRID 2076437 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][CH:27]=[C:26]([NH2:30])[CH:25]=1.CCN(CC)CC>O=S(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl.[NH4+].[Cl-]>[F:20][C:2]([F:1])([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([CH3:17])([CH3:16])[CH2:11][CH2:10][C:9]2([CH3:18])[CH3:19])[C:3]([NH:30][C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][CH:27]=1)[C:23]([O:22][CH3:21])=[O:31])=[O:5]

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 78274Benzoic acid, 3-amino-, methyl esterHCID 23075286HCID 23075286, compound

Product 1

HCID 23075289HCID 23075289, compoundYield 70%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolventHCID 25517Ammonium 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 (0.53 g, 1.88 mmol) was dissolved in SOCl2 and two drops of DMF were added at 0° C. The mixture was stirred at 0° C. for 0.5 h, evaporated and the crude product was dissolved in CH2Cl2 (5 mL). B) Methyl-3-aminobenzoate (284 mg, 1.88 mmol) and DMAP (23 mg, 0.19 mmol) were dissolved in CH2Cl2 (5 mL) and Et3N (2.6 mL) was added at 0° C. A) was added in B) at 0° C. and this mixture was stirred at 0° C. for 10 min and abandoned at RT for 1 h. The mixture was poured in aqueous NH4Cl 5% (100 mL) and extracted with EtOAc (3×50 mL). The organic layer was washed with NaHCO3 (2×100 mL), brine (2×100 mL), dried with MgSO4, filtered and evaporated. The crude product was purified by column chromatography using as eluent cyclohexane:EtOAc=90:10.Methyl 3-(2,2-difluoro-2-(1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalen-6-yl)acetamido)benzoate 19 was obtained (0.55 g, 70% yield) as a yellow oil.

Workup

  1. customevaporated
  2. dissolutionthe crude product was dissolved in CH2Cl2 (5 mL)
  3. additionA) was added in B) at 0° C.
  4. stirringthis mixture was stirred at 0° C. for 10 min
  5. waitabandoned at RT for 1 h
  6. extractionextracted with EtOAc (3×50 mL)
  7. washThe organic layer was washed with NaHCO3 (2×100 mL), brine (2×100 mL)
  8. dry with materialdried with MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-6b38e0679e5a42d4839e3ab488ad224c
Source dataset
uspto-grants-2011_04
Patent number
US07923579B2

Reaction notes

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