N-(Diphenylmethylene)glycine tert-butyl ester → 2-(Benzhydrylidene-amino)-3-(2-fluoro-5-methoxy-phenyl)-propionic acid tert-butyl ester

HRID 1242858Notes

Reaction equation

HRID 1242858 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:11]([O:15][C:16](=[O:32])[CH2:17][N:18]=[C:19]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([CH3:14])([CH3:13])[CH3:12].Br[CH2:34][C:35]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:36]=1[F:43]>C1(C)C=CC=CC=1.C1COCC1.CCOCC.CCCCC>[C:11]([O:15][C:16](=[O:32])[CH:17]([N:18]=[C:19]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[CH2:34][C:35]1[CH:40]=[C:39]([O:41][CH3:42])[CH:38]=[CH:37][C:36]=1[F:43])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 3

HCID 688171N-(Diphenylmethylene)glycine tert-butyl esterHCID 3251421Potassium bis(trimethylsilyl)amideHCID 218916842-(Bromomethyl)-1-fluoro-4-methoxybenzene

Product 1

HCID 879214182-(Benzhydrylidene-amino)-3-(2-fluoro-5-methoxy-phenyl)-propionic acid tert-butyl esterYield 22%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×HCID 21877078Diethylether pentaneSolvent

Procedure

KHMDS (550 μl of a 0.5 M solution in toluene, 0.55 mmol) diluted with dry THF (1.5 mL) was added to a solution of t-butylglycinate Schiff base 3 (68 mg, 0.23 mmol) in THF (1.5 mL). A mixture containing 2-fluoro-5-methoxybenzyl bromide (35, 50 mg, 0.23 mmol) in THF (1.0 mL) was immediately added to the resulting enolate solution at −78° C. The combined mixture was warmed to room temperature, stirred for 2 h, diluted with 1:1 ether/pentane (20 mL), washed with brine (3×10 mL), dried (sodium sulfate), filtered and then concentrated to afford 40 as a crude yellow oil (115%). Interestingly, a lower yield of 22% (40 mg) was obtained compared to using LiHMDS.

Workup

  1. washwashed with brine (3×10 mL)
  2. dry with materialdried (sodium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-a70fcce98c6b45239a24a6072f23a4a5
Source dataset
uspto-grants-2006_10
Patent number
US07115766B2

Reaction notes

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