Sodium hydride → 4-Benzyl 1,4-di-tert-butyl (1S)-6-[4-(benzyloxy)phenyl]-1-[(tert-butoxycarbonyl)amino]hexane-1,4,4-tricarboxylate

HRID 591312Notes

Reaction equation

HRID 591312 reaction equation
[CH2:1]([O:8][C:9]([CH:11]([CH2:19][CH2:20][C@H:21]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:39]([O:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:53][CH2:54]Br)=[CH:49][CH:48]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>CN(C)C=O>[CH2:39]([O:46][C:47]1[CH:48]=[CH:49][C:50]([CH2:53][CH2:54][C:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:19][CH2:20][C@H:21]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])=[CH:51][CH:52]=1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 166388271-(Benzyloxy)-4-(2-bromoethyl)benzeneHCID 117812690Di-tert-butyl (5S)-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)amino]hexanedioate

Product 1

HCID 1178127014-Benzyl 1,4-di-tert-butyl (1S)-6-[4-(benzyloxy)phenyl]-1-[(tert-butoxycarbonyl)amino]hexane-1,4,4-tricarboxylateYield 26.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1.11 g di-tert-butyl (5S)-2-(benzyloxycarbonyl)-5-[(tert-butoxycarbonyl)-amino]hexanedioate (2.19 mmol; see example 12f) in N,N-dimethyl formamide (30 mL) was added under argon atmosphere 96 mg of sodium hydride (60% in oil, 2.40 mmol), and the mixture was stirred for 30 min at room temperature. Subsequently, a solution of 700 mg of 1-(benzyloxy)-4-(2-bromoethyl)benzene (2.40 mmol) in N,N-dimethyl formamide (15 mL) was added, an the mixture was stirred at 60° C. for 3 hours. The mixture was concentrated in vacuo, partitioned between water and ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by preparative HPLC (Method A) to give 413 mg of the target compound in approx. 90% purity (26% purity adjusted yield).

Workup

  1. stirringan the mixture was stirred at 60° C. for 3 hours
  2. concentrationThe mixture was concentrated in vacuo
  3. custompartitioned between water and ethyl acetate
  4. washthe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by preparative HPLC (Method A)

Sources & evidence

ORD record
ord-01550c4e4a11426e9ab6ebbfc73410db
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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