Ammonium Chloride → 4-(2-Fluoro-3-methoxyphenyl)-2-hydroxy-4-methylpentanoic acid methyl ester

HRID 1869333Notes

Reaction equation

HRID 1869333 reaction equation
[CH3:1][O:2][C:3](=[O:18])[CH2:4][CH2:5][C:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[C:10]=1[F:17])([CH3:8])[CH3:7].C1(S(N2C(C3C=CC=CC=3)O2)(=O)=[O:26])C=CC=CC=1.[Cl-].[NH4+]>C1(C)C=CC=CC=1.O1CCCC1>[CH3:1][O:2][C:3](=[O:18])[CH:4]([OH:26])[CH2:5][C:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[C:10]=1[F:17])([CH3:8])[CH3:7]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 3204052-(Benzenesulfonyl)-3-phenyloxaziridineHCID 179893004-(2-Fluoro-3-methoxyphenyl)-4-methylpentanoic acid methyl ester

Product 1

HCID 179890874-(2-Fluoro-3-methoxyphenyl)-2-hydroxy-4-methylpentanoic acid methyl esterYield 58.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

19.58 g (77 mmol) of 4-(2-fluoro-3-methoxyphenyl)-4-methylpentanoic acid methyl ester is introduced into 245 ml of tetrahydrofuran, and the reaction mixture is cooled to −70° C. Within one hour, 220.7 ml of a 0.5 molar solution of potassium-bis-(trimethylsilylamide) in toluene is added in drops, and the reaction mixture is then stirred for 45 more minutes at −70° C. 28.3 g (107.79 mmol) of Davis reagent, dissolved in 245 ml of tetrahydrofuran, is now added in drops within 40 minutes. After two hours of stirring at −70° C., 250 ml of saturated ammonium chloride solution is slowly added in drops, and in this case, the batch is brought to room temperature. After extraction with methyl tert-butyl ether, the combined organic extracts are treated as usual with water and brine. After the solvent is spun off, the residue is chromatographed several times on silica gel (mobile solvent ethyl acetate/hexane). 12.14 g (58.3%) of the desired compound is ultimately isolated.

Workup

  1. additionis now added in drops within 40 minutes
  2. stirringAfter two hours of stirring at −70° C.
  3. customis brought to room temperature
  4. extractionAfter extraction with methyl tert-butyl ether
  5. additionthe combined organic extracts are treated as usual with water and brine
  6. customthe residue is chromatographed several times on silica gel (mobile solvent ethyl acetate/hexane)

Sources & evidence

ORD record
ord-058a1c561b37498ca7b8089dc27cc2a5
Source dataset
uspto-grants-2009_12
Patent number
US07638515B2

Reaction notes

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