Triethylamine → 2-Ethoxycarbonyl-2,2-difluoro-1-phenylethyl 1-adamantanecarboxylate

HRID 1506736Notes

Reaction equation

HRID 1506736 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>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:17]12([C:27]([O:15][CH:8]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])([F:16])[F:1])=[O:28])[CH2:24][CH:23]3[CH2:22][CH:21]([CH2:20][CH:19]([CH2:25]3)[CH2:18]1)[CH2:26]2

Participants

6

Reactant 3

HCID 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 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

In 60 g of methylene chloride were dissolved 9 g of ethyl 2,2-difluoro-3-hydroxy-3-phenylpropionate, prepared in Synthesis Example 1-4, and 9.5 g of 1-adamantanecarbonyl chloride. Under ice cooling, a mixture of 6 g of triethylamine, 0.5 g of 4-dimethylaminopyridine and 20 g of methylene chloride was added dropwise to the solution. The reaction solution was aged overnight, after which it was quenched with 5 wt % hydrochloric acid, washed with water, and concentrated. Methyl isobutyl ketone was added to the concentrate, which was concentrated again. There was obtained 15 g of the target compound, 2-ethoxycarbonyl-2,2-difluoro-1-phenylethyl 1-adamantanecarboxylate as colorless oily matter (yield 68%).

Workup

  1. additionwas added dropwise to the solution
  2. customafter which it was quenched with 5 wt % hydrochloric acid
  3. washwashed with water
  4. concentrationconcentrated
  5. additionMethyl isobutyl ketone was added to the concentrate, which
  6. concentrationwas concentrated again

Sources & evidence

ORD record
ord-a4d8b01fb6954133a2afec85748c072e
Source dataset
uspto-grants-2015_12
Patent number
US09221742B2

Reaction notes

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