1-Hydroxybenzotriazole → methyl (RS)-3-hydroxy-2-[4-(3-thienylmethoxy)-2-(2-trimethylsilylethoxymethoxy)benzoyl]aminopropionate

HRID 322971Notes

Reaction equation

HRID 322971 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([CH2:6][O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[C:10]([O:17][CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=2)=[CH:2]1.Cl.[CH3:27][O:28][C:29](=[O:34])[CH:30]([CH2:32][OH:33])[NH2:31].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.C(N(CC)CC)C>[OH:33][CH2:32][CH:30]([NH:31][C:12](=[O:14])[C:11]1[CH:15]=[CH:16][C:8]([O:7][CH2:6][C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)=[CH:9][C:10]=1[O:17][CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:29]([O:28][CH3:27])=[O:34]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 517373Methyl DL-serinate hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220102164-(3-Thienylmethoxy)-2-(2-trimethylsilylethoxy)methoxybenzoic acid

Product 1

HCID 86756595methyl (RS)-3-hydroxy-2-[4-(3-thienylmethoxy)-2-(2-trimethylsilylethoxymethoxy)benzoyl]aminopropionateYield 85.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 4-(3-thienylmethoxy)-2-(2-trimethylsilylethoxymethoxy)benzoic acid (6 g), (RS) serine methyl ester hydrochloride (2.7 g), 1-hydroxybenzotriazole (2.6 g), triethylamine (2.4 mL), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (3.6 g) and DMF (100 mL) is stirred at ambient temperature for 16 hours. The reaction is concentrated in vacuo and the residue partitioned between ethyl acetate (150 mL) and 1N HCl (100 mL). The organic phase is washed with water (2×100 mL) then dried over magnesium sulphate, filtered and concentrated in vacuo. The residue is purified by flash chromatography on silica eluting initially with a mixture of ethyl acetate and cyclohexane (3:7 v/v) then with a mixture of ethyl acetate and cyclohexane (1:1 v/v). Fractions homogeneous in the required product are combined and evaporated to give methyl (RS)-3-hydroxy-2-[4-(3-thienylmethoxy)-2-(2-trimethylsilylethoxymethoxy)benzoyl]aminopropionate (6.5 g) as a colourless oil.

Workup

  1. concentrationThe reaction is concentrated in vacuo
  2. customthe residue partitioned between ethyl acetate (150 mL) and 1N HCl (100 mL)
  3. washThe organic phase is washed with water (2×100 mL)
  4. dry with materialthen dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash chromatography on silica eluting initially with a mixture of ethyl acetate and cyclohexane (3:7 v/v)
  8. additionwith a mixture of ethyl acetate and cyclohexane (1:1 v/v)
  9. customevaporated

Sources & evidence

ORD record
ord-6e1c5441e93c48e0828af71df3d2da76
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Reaction notes

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