Methanol → Methyl 5-chloro-2-fluoro-4-((3-(hydroxymethyl)-adamantan-1-yl)methoxy)benzoate

HRID 1849705Notes

Reaction equation

HRID 1849705 reaction equation
[Cl:1][C:2]1[C:3]([O:12][CH2:13][C:14]23[CH2:23][CH:18]4[CH2:19][CH:20]([CH2:22][C:16]([CH2:24][OH:25])([CH2:17]4)[CH2:15]2)[CH2:21]3)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].CO.[CH2:28](N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([O:12][CH2:13][C:14]23[CH2:23][CH:18]4[CH2:19][CH:20]([CH2:22][C:16]([CH2:24][OH:25])([CH2:17]4)[CH2:15]2)[CH2:21]3)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([O:9][CH3:28])=[O:8]

Participants

7

Reactant 3

HCID 887MethanolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 867035785-Chloro-2-fluoro-4-((3-(hydroxymethyl)adamantan-1-yl)methoxy)benzoic acid

Product 1

HCID 86703577Methyl 5-chloro-2-fluoro-4-((3-(hydroxymethyl)-adamantan-1-yl)methoxy)benzoateYield 18%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-chloro-2-fluoro-4-((3-(hydroxymethyl)adamantan-1-yl)methoxy)benzoic acid (3.53 g, 9.57 mmol), 4-dimethylaminopyridine (0.23 g, 1.90 mmol), and methanol (3.87 mL, 95.70 mmol) in anhydrous dimethylformamide (50 mL) under nitrogen was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (3.67 g, 19.10 mmol). The reaction mixture was stirred for 24 hours at ambient temperature; diluted with ethyl acetate (200 mL) and washed with water (100 mL), saturated ammonium chloride (100 mL), and brine (100 mL); dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (3:1 hexanes:ethyl acetate) to provide the title compound (0.65 g, 18%): 1H NMR (300 MHz, CDCl3) δ 7.90 (d, J=7.9 Hz, 1H), 6.59 (d, J=12.6 Hz, 1H), 3.85 (s, 3H), 3.56 (s, 2H), 3.23 (s, 2H), 2.11 (br s, 1H), 1.74-1.40 (m, 14H); MS (ES+) m/z 383.1, 385.1 (M+1).

Workup

  1. washwashed with water (100 mL), saturated ammonium chloride (100 mL), and brine (100 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (3:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-9bd29afc9b2146019b342876c685aed9
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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