Hydrochloric Acid → 2-Ethoxycarbonyl-2,2-difluoro-1-phenylethyl 1-adamantanecarboxylate

HRID 58517

Reaction equation

HRID 58517 reaction equation
[F:1][C:2]([F:16])([CH:8]([OH:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:17]12([C:27](Cl)=[O:28])[CH2:26][CH:21]3[CH2:22][CH:23]([CH2:25][CH:19]([CH2:20]3)[CH2:18]1)[CH2:24]2.C(N(CC)CC)C.Cl>C(Cl)Cl>[CH2:6]([O:5][C:3]([C:2]([F:16])([F:1])[CH:8]([O:15][C:27]([C:17]12[CH2:26][CH:21]3[CH2:20][CH:19]([CH2:25][CH:23]([CH2:22]3)[CH2:24]1)[CH2:18]2)=[O:28])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:4])[CH3:7]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 989151-Adamantanecarbonyl chlorideHCID 11138943Ethyl 2,2-difluoro-3-hydroxy-3-phenylpropanoate

Product 1

HCID 1179666922-Ethoxycarbonyl-2,2-difluoro-1-phenylethyl 1-adamantanecarboxylateYield 97.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Ethyl 2,2-difluoro-3-hydroxy-3-phenylpropionate acid (9 g) prepared in Synthesis Example 1-4 and 1-adamantanecarbonyl chloride (9.5 g) were dissolved in methylene chloride (60 g), and a mixed solution of triethyl amine (6 g), 4-dimethyl aminopyridine (0.5 g) and methylene chloride (20 g) was dropped into the obtained solution under ice cooling. After aging overnight, 5% by mass hydrochloric acid was added to the product and quenched, and then the reaction solution was washed with water, and concentrated. Methylisobutyl ketone was added to the concentrated solution, and was concentrated again to obtain a target compound, or 1-adamantane carboxylic acid 2-ethoxycarbonyl-2,2-difluoro-1-phenyl-ethyl ester (15 g) as a colorless oily matter (yield: 68%).

Workup

  1. customquenched
  2. washthe reaction solution was washed with water
  3. concentrationconcentrated
  4. additionMethylisobutyl ketone was added to the concentrated solution
  5. concentrationwas concentrated again

Sources & evidence

ORD record
ord-b559aa3f57f942a1bb5d1fd0236eb0b3
Source dataset
uspto-grants-2016_09
Patent number
US09436083B2

Linked notes

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