Triethylamine → 3-[3-(1-Benzyloxycarbonylamino-3-methyl-butyl)-isoxazol-5-yl]-propionic acid methyl ester

HRID 277189Notes

Reaction equation

HRID 277189 reaction equation
[CH2:1]([O:8][C:9](=[O:19])[NH:10][CH:11]([CH:16]=[N:17][OH:18])[CH2:12][CH:13]([CH3:15])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][O:21][C:22](=[O:27])[CH2:23][CH2:24][C:25]#[CH:26].C(N(CC)CC)C>C(Cl)Cl>[CH3:20][O:21][C:22](=[O:27])[CH2:23][CH2:24][C:25]1[O:18][N:17]=[C:16]([CH:11]([NH:10][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:19])[CH2:12][CH:13]([CH3:15])[CH3:14])[CH:26]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 543061Methyl 4-pentynoateHCID 73456130[1-(Hydroxyimino-methyl)-3-methyl-butyl]-carbamic acid benzyl ester

Product 1

HCID 186823663-[3-(1-Benzyloxycarbonylamino-3-methyl-butyl)-isoxazol-5-yl]-propionic acid methyl esterYield 29.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of [1-(hydroxyimino-methyl)-3-methyl-butyl]-carbamic acid benzyl ester (6.0 g, 22.7 mmol) and pent-4-ynoic acid methyl ester (3.8 g, 34 mmol) in CH2Cl2 (80 ml) was added triethylamine (0.2 ml) followed by Clorox bleach (80 ml). After 4 h at room temperature the organic phase was separated and the aqueous phase was extracted with CH2Cl2 (25 ml×3). The combined organics were dried over MgSO4; filtered and concentrated under reduced pressure to give a yellow oil. Purification by Flash 40 chromatography using a silica gel column and eluting with 10-20% EtOAc/hexane gave 2.5 g of the title compound as a waxy pale yellow solid. MS [M+1]+375.3; 1H nmr (400 MHz, CDCl3) δ0.91 (m, 6H), 1.51-1.76 (m, 3H), 2.67 (t, J=7.5 Hz, 2H), 3.02 (t, J=7.5 Hz, 2H), 3.67 (s, 3H), 4.89 (m,1H), 5.08 (m, 3H), 5.92 (s, 1H), 7.31 (m, 5H).

Workup

  1. customAfter 4 h at room temperature the organic phase was separated
  2. extractionthe aqueous phase was extracted with CH2Cl2 (25 ml×3)
  3. dry with materialThe combined organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give a yellow oil
  7. customPurification by Flash 40 chromatography
  8. washeluting with 10-20% EtOAc/hexane

Sources & evidence

ORD record
ord-fa3c518b4c5e4061b286a9d6731fa3fc
Source dataset
uspto-grants-2002_03
Patent number
US06355662B1

Reaction notes

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