Triethylamine → 4-Methyl-1,3-dioxol-2-one-5-ylmethyl(S)N-(t-Butoxycarbonyl)-3-hydroxy-alpha-methyltyrosinate

HRID 1906710Notes

Reaction equation

HRID 1906710 reaction equation
[C:1]([O:5][C:6]([NH:8][C@:9]([CH3:22])([C:19]([OH:21])=[O:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([OH:18])[CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.Br[CH2:31][C:32]1[O:33][C:34](=[O:38])[O:35][C:36]=1[CH3:37]>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][C@:9]([CH3:22])([C:19]([O:21][CH2:37][C:36]1[O:35][C:34](=[O:38])[O:33][C:32]=1[CH3:31])=[O:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([OH:18])[CH:12]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 107741414-(Bromomethyl)-5-methyl-1,3-dioxol-2-oneHCID 15719345(2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid

Product 1

HCID 1317150874-Methyl-1,3-dioxol-2-one-5-ylmethyl(S)N-(t-Butoxycarbonyl)-3-hydroxy-alpha-methyltyrosinateYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-(t-butoxycarbonyl)-3-hydroxy-α-methyltyrosine (760 mg, 2.44 mmol), triethylamine (263 mg, 2.60 mmol) and 4-bromomethyl-5-methyl-1,3-dioxol-2-one (500 mg, 2.60 mmol) in dimethylformamide, 10 mL, is stirred at 60° C. for 3 hours under nitrogen. Most of the dimethylformamide is removed at 50°-60° C. and 0.1 mm and the residue is partitioned between saturated sodium bicarbonate solution, 10 mL, and ethyl acetate, 50 mL. The ethyl acetate extract is washed with water saturated with sodium sulfate, filtered and concentrated at 40°-45° C. and 15 mm. Flash chromatography of the residue over 40 g of silica gel 60 (230-400 mesh) with 3% methanol-97% chloroform as eluent affords 320 mg of the desired ester.

Workup

  1. customMost of the dimethylformamide is removed at 50°-60° C.
  2. custom0.1 mm and the residue is partitioned between saturated sodium bicarbonate solution, 10 mL, and ethyl acetate, 50 mL
  3. extractionThe ethyl acetate extract
  4. washis washed with water saturated with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated at 40°-45° C.

Sources & evidence

ORD record
ord-36018ca2a034414b8916320a13fbcf43
Source dataset
uspto-grants-1987_03
Patent number
US04654331

Reaction notes

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