Benzyl Bromide → di-tert-butyl (5S)-2-[4-(benzyloxy)benzyl]-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioate

HRID 591317Notes

Reaction equation

HRID 591317 reaction equation
[C:1]([O:5][C:6](=[O:36])[C@H:7]([C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])[CH2:8][CH2:9][CH:10]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:39](Br)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>CN(C)C=O>[C:14]([O:13][C:11](=[O:12])[C@@H:10]([NH:18][C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:9][CH2:8][C:7]([C:26]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:27])([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:36])[CH2:39][C:40]1[CH:45]=[CH:44][C:43]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:42][CH:41]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 131734511(2S)-2-Benzyloxycarbonyl-5-tert.-butoxycarbonylamino-hexane dioic acid di-tert.-butyl ester

Product 1

HCID 70977725di-tert-butyl (5S)-2-[4-(benzyloxy)benzyl]-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioateYield 157.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.00 g (1.97 mmol) (2S)-2-Benzyloxycarbonyl-5-tert.-butoxycarbonylamino-hexane dioic acid di-tert.-butyl ester were dissolved in 25 mL dimethylformamide, 87 mg (2.2 mmol) NaH (60% in mineral oil) added and stirred at room temperature for 30 min. 601 mg (2.17 mmol) 4-benzloxy benzyl bromide 1 mL dimethylformamide were added and the reaction stirred for 1 h at 60° C. The solvent was removed i. vac. And the residue partitioned between ethyl acetate and brine. The organic phase was adsorbed on Isolute and directly chromatographed on a Biotage Isolera system (SNAP 100 g, A=n-Hexane, B=ethyl acetate. A 3 CV, A to 25% B in 10 CV, 4.7 CV 25% B, 50 mL/min, Fr. a 18 mL). Fractions 68 to 75 were collected to give 1.09 g (79%) of (2S,5SR)-5-Benzyloxycarbonyl-6-(4-benzyloxy-phenyl)-5-tert.-butoxycarbonyl-2-tert.-butoxycarbonylamino-hexanoic acid tert.-butyl ester.

Workup

  1. stirringthe reaction stirred for 1 h at 60° C
  2. customThe solvent was removed i
  3. customAnd the residue partitioned between ethyl acetate and brine
  4. customdirectly chromatographed on a Biotage Isolera system (SNAP 100 g
  5. customFractions 68 to 75 were collected

Sources & evidence

ORD record
ord-be19a609ef1543a5af5272345ba179a9
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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