Triethylamine → HCID 60152317, compound

HRID 2404597Notes

Reaction equation

HRID 2404597 reaction equation
[CH3:1][N:2]([CH2:4][CH:5]1[CH2:11][CH2:10][CH:9]2[CH:7]([CH2:8]2)[C:6]1([C:13]1[CH:18]=[C:17]([OH:19])[CH:16]=[C:15]([F:20])[CH:14]=1)[OH:12])[CH3:3].[CH3:21][C:22]([CH3:27])([CH3:26])[C:23](Cl)=[O:24].C(N(CC)CC)C>C(Cl)Cl>[CH3:3][N:2]([CH2:4][CH:5]1[CH2:11][CH2:10][CH:9]2[CH:7]([CH2:8]2)[C:6]1([C:13]1[CH:18]=[C:17]([O:19][C:23](=[O:24])[C:22]([CH3:27])([CH3:26])[CH3:21])[CH:16]=[C:15]([F:20])[CH:14]=1)[OH:12])[CH3:1]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 60152194HCID 60152194, compound

Product 1

HCID 60152317HCID 60152317, compoundYield 59.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Stir a mixture of 3-dimethylaminomethyl-2-(3-fluoro-5-hydroxy-phenyl)-bicyclo[4.1.0]heptan-2-ol (295 mg, 1.06 mmol), 2,2-dimethyl-propionyl chloride (153 mg, 1.27 mmol) and triethyl-amine (321 mg, 3.18 mmol) in CH2Cl2 (40 mL) at ambient temperature for 5 hours. Quench the mixture with 10 mL of H2O, Separate the aqueous layer off, and concentrate the organic layer under reduced pressure. Purify the residue by preparative TLC to give 2,2-dimethyl-propionic acid 3-(3-dimethylaminomethyl-2-hydroxy-bicyclo[4.1.0]hept-2-yl)-5-fluoro-phenyl ester as white solid (228 mg, Yield: 59.2%). MS (m/z): 364 (M+1). 1H NMR (400 MHz, Methanol-d4) δ 7.25-7.28 (d, J1=10.4, J2=1.6, 1H), 7.14 (s, 1H), 6.76-6.78 (d, J1=9.2, J2=2.4, 1H), 2.37-2.46 (m, 1H), 2.15-2.19 (m, 7H), 1.99-2.03 (d, J=13.2, 1H), 1.82 (m, 2H), 1.53-1.68 (m, 2H), 1.37 (s, 9H), 1.17 (m, 1H), 1.01-1.06 (m, 1H), 0.75-0.81 (m, 1H), 0.48-0.50 (m, 1H).

Workup

  1. customQuench the mixture with 10 mL of H2O
  2. customSeparate the aqueous layer off, and
  3. concentrationconcentrate the organic layer under reduced pressure
  4. customPurify the residue by preparative TLC

Sources & evidence

ORD record
ord-1cd61b00036c4bb1b7e16f5ae369626d
Source dataset
uspto-grants-2014_08
Patent number
US08802728B2

Reaction notes

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