Allyl bromide → N-Boc-O-allyl-L-homoserine

HRID 346965Notes

Reaction equation

HRID 346965 reaction equation
[H-].[Na+].[CH3:3][C:4]([O:7][C:8]([NH:10][C@H:11]([C:15]([OH:17])=[O:16])[CH2:12][CH2:13][OH:14])=[O:9])([CH3:6])[CH3:5].[CH2:18](Br)[CH:19]=[CH2:20]>CN(C=O)C>[CH2:20]([O:14][CH2:13][CH2:12][C@H:11]([NH:10][C:8]([O:7][C:4]([CH3:3])([CH3:5])[CH3:6])=[O:9])[C:15]([OH:17])=[O:16])[CH:19]=[CH2:18]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 13066457(2S)-2-(((tert-butoxy)carbonyl)amino)-4-hydroxybutanoic acid

Product 1

HCID 58798660N-Boc-O-allyl-L-homoserineYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of sodium hydride (913 mg, 22.8 mmoL) in DMF at 0° C. was added N-t-Boc-L-homoserine (2 g, 9.13 mmoL). This reaction mixture was stirred at 0° C. for 15 min, and then allyl bromide (1.38 g, 11.4 mmoL) was added. The mixture was warmed up to rt, and stirred for 2 h. It was then concentrated in vacuo. The residue was diluted with water, and sequentially washed with hexane and ether. The organic layers were discarded, and the aqueous layer was carefully adjusted to pH 3 with 1 N HCl. This acidic aqueous solution was extracted with ethyl acetate. The organic phase was dried (MgSO4), and concentrated in vacuo to yield 2.2 g (93%) of (S)-4-allyloxy-2-(tert-butoxycarbonylamino)butyric acid as a colorless oil. 1H NMR (300 MHz, CD3OD) δ 1.42 (s, 9H), 1.80–1.90 (m, 1H), 2.04–2.16 (m, 1H), 3.50–3.54 (m, 2H), 3.97 (d, J=0.39 Hz, 2H), 4.23 (dd, J=8.78, 4.39 Hz, 1H), 5.15 (d, J=10.25 Hz, 1H), 5.26 (dd, J=17.38, 1.65 Hz, 1H), 5.84–5.97 (m, 1H). This starting material was employed in the synthesis of (1R,2S)-ethyl 1-((3R,5S)-1-((S)-4-(allyloxy)-2-(tert-butoxycarbonyl)butanoyl)-3-(6-methoxyisoquinolin-1-yloxy)pyrrolidine-5-carboxamido)-2-vinylcyclopropane-carboxylate as described in example 2.

Workup

  1. temperatureThe mixture was warmed up to rt
  2. stirringstirred for 2 h
  3. concentrationIt was then concentrated in vacuo
  4. additionThe residue was diluted with water
  5. washsequentially washed with hexane and ether
  6. extractionThis acidic aqueous solution was extracted with ethyl acetate
  7. dry with materialThe organic phase was dried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-78320c418cce4b8ab60220ffa3b92168
Source dataset
uspto-grants-2007_02
Patent number
US07173004B2

Reaction notes

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