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

HRID 1242856Notes

Reaction equation

HRID 1242856 reaction equation
[C:1]([O:5][C:6](=[O:22])[CH2:7][N:8]=[C:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C1COCC1.CN1C(=O)N(C)CCC1.[Li+].CC([N-]C(C)C)C.Br[CH2:46][C:47]1[CH:52]=[C:51]([O:53][CH3:54])[CH:50]=[CH:49][C:48]=1[F:55]>C1COCC1>[C:1]([O:5][C:6](=[O:22])[CH:7]([N:8]=[C:9]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:46][C:47]1[CH:52]=[C:51]([O:53][CH3:54])[CH:50]=[CH:49][C:48]=1[F:55])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 688171N-(Diphenylmethylene)glycine tert-butyl esterHCID 2724682Lithium diisopropylamideHCID 218916842-(Bromomethyl)-1-fluoro-4-methoxybenzeneHCID 22565281tetrahydrofuran 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone

Product 1

HCID 879214182-(Benzhydrylidene-amino)-3-(2-fluoro-5-methoxy-phenyl)-propionic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

t-Butylglycinate Schiff base 3 (136 mg, 0.46 mmol) in a mixture of dry THF-DMPU 60:40 (2.5 mL) at −78° C. was treated with a 2.0 M LDA solution (0.23 mL, 0.46 mmol) and the mixture was stirred for one h at the same temperature. 2-Fluoro-5-methoxybenzyl bromide (35, 100 mg, 0.46 mmol) in dry THF (2.5 mL) was added dropwise at −78° C. and then the mixture was stirred overnight at room temperature. The reaction was quenched with saturated aqueous ammonium chloride (10 mL), and the product was extracted with diethyl ether (2×15 mL). The combined organic layers were washed with saturated aqueous ammonium chloride (4×10 mL), dried over sodium sulfate, filtered and evaporated to give 40 as a crude yellow oil (110%). When examined, the pure product 40 was made in 80% yield (175 mg).

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. customThe reaction was quenched with saturated aqueous ammonium chloride (10 mL)
  3. extractionthe product was extracted with diethyl ether (2×15 mL)
  4. washThe combined organic layers were washed with saturated aqueous ammonium chloride (4×10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-2783b651647e40c396285dfcc2999456
Source dataset
uspto-grants-2006_10
Patent number
US07115766B2

Reaction notes

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