Triethylamine → HCID 23075283, compound

HRID 2076441Notes

Reaction equation

HRID 2076441 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](O)=[O:4].[NH2:21][CH2:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=1.CCN(CC)CC.[NH4+].[Cl-]>O=S(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:1][C:2]([F:20])([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:21][CH2:22][C:23]1[CH:24]=[CH:25][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:31][CH:32]=1)=[O:4]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 571728Methyl 4-(aminomethyl)benzoateHCID 23075286HCID 23075286, compound

Product 1

HCID 23075283HCID 23075283, compoundYield 58%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
0 °C

Procedure

Difluoro-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-acetic acid 16 (306 mg, 1.08 mmol) was dissolved in SOCl2 and two drops of DMF were added at 0° C. The mixture was stirred at 0° C. for 30 min then evaporated and the product was dissolved in CH2Cl2 (7 mL). B) Methyl 4-(aminomethyl)benzoate SLA 07006 (179 mg, 1.08 mmol) and DMAP (14 mg, 0.11 mmol) were dissolved in CH2Cl2 (7 mL) and Et3N (1.5 mL) at 0° C. A) was added at 0° C. via syringe in B) and the resulting mixture was stirred at 0° C. for 10 min and abandoned at RT for 1 h. Aqueous NH4Cl 5% (100 mL) was added and the mixture extracted with EtOAc (3×50 mL). The organic layer was washed with NaHCO3 5% (3×100 mL) and brine (3×100 mL), dried over MgSO4, filtered and evaporated in vacuo. The crude product was purified by flash chromatography using as eluent cyclohexane:EtOAc=9:1. Methyl 4-((2,2-difluoro-2-(1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalen-6-yl)acetamido)methyl)-benzoate 21 was obtained (0.27 g, 58% yield) as a beige solid.

Workup

  1. customthen evaporated
  2. dissolutionthe product was dissolved in CH2Cl2 (7 mL)
  3. customat 0° C
  4. additionA) was added at 0° C. via syringe in B) and the resulting mixture
  5. stirringwas stirred at 0° C. for 10 min
  6. waitabandoned at RT for 1 h
  7. extractionthe mixture extracted with EtOAc (3×50 mL)
  8. washThe organic layer was washed with NaHCO3 5% (3×100 mL) and brine (3×100 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-df4818df37ba46bea0bcb911ed45126b
Source dataset
uspto-grants-2011_04
Patent number
US07923579B2

Reaction notes

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