Hydrochloric Acid → di-tert-butyl (4S)-4-{4-[2-(benzyloxy)ethoxy]-3-tert-butoxybenzyl}-N-(tert-butoxycarbonyl)-L-glutamate

HRID 591325Notes

Reaction equation

HRID 591325 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:36]([O:43][CH2:44][CH2:45][O:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:53]Br)=[CH:49][C:48]=1[O:55][C:56]([CH3:59])([CH3:58])[CH3:57])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.Cl>C1COCC1>[CH2:36]([O:43][CH2:44][CH2:45][O:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:53][C@H:11]([C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])[CH2:10][C@@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[CH:49][C:48]=1[O:55][C:56]([CH3:59])([CH3:58])[CH3:57])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 86647571Di-tert-butyl Boc-L-glutamateHCID 1177786181-[2-(Benzyloxy)ethoxy]-4-(bromomethyl)-2-tert-butoxybenzene

Product 1

HCID 117812703di-tert-butyl (4S)-4-{4-[2-(benzyloxy)ethoxy]-3-tert-butoxybenzyl}-N-(tert-butoxycarbonyl)-L-glutamateYield 48.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 327 mg (0.91 mmol) di-tert-butyl N-(tert-butoxycarbonyl)-L-glutamate in 10 ml THF was added 2 ml (2 mmol) lithium bis(trimethylsilyl)amide solution in THF drop by drop at −78° C. The reaction mixture was stirred for 2 hours. 300 mg (0.76 mmol) 1-[2-(benzyloxy)ethoxy]-4-(bromomethyl)-2-tert-butoxybenzene in 2 ml THF were added at −78° C. The reaction mixture was stirred for 2 hours. 4.5 ml aqueous hydrogen chloride solution (2N) is added drop by drop. The solution was allowed to be warmed to room temperature. The solution was extracted repeatedly with dichloro methane. The combined organic phases were washed with water, dried with sodium sulfate and concentrated in vacuo. The crude product is purified twice by column chromatography (silica gel, hexane/ethylacetate gradient: 7:1→1:1). The desired product was obtained in 48.7% yield (358 mg, 0.45 mmol).

Workup

  1. stirringThe reaction mixture was stirred for 2 hours
  2. extractionThe solution was extracted repeatedly with dichloro methane
  3. washThe combined organic phases were washed with water
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified twice by column chromatography (silica gel, hexane/ethylacetate gradient: 7:1→1:1)

Sources & evidence

ORD record
ord-4593e93358064d1c9b0cb8d09b4f6419
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

Loading…