Chloromethyl Ethyl Carbonate → HCID 68719474, compound

HRID 2246703Notes

Reaction equation

HRID 2246703 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C@@H:13]([OH:25])[CH2:14][P:15]([CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)(=[O:17])[OH:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:26]([O:28][C:29](=[O:33])[O:30][CH2:31]Cl)[CH3:27]>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[CH2:26]([O:28][C:29]([O:30][CH2:31][O:17][P:15]([CH2:14][CH:13]([OH:25])[CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10])([CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)=[O:16])=[O:33])[CH3:27]

Participants

5

Reactant 2

HCID 5325479Chloromethyl Ethyl CarbonateHCID 68719246HCID 68719246, compound

Product 1

HCID 68719474HCID 68719474, compoundYield 23.2%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 1140TolueneSolvent

Procedure

To a solution of ((R)-3-benzyloxycarbonylamino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid (1.0 g, 2.71 mmol) and carbonic acid chloromethyl ester ethyl ester (1.13 g, 8.16 mmol) in toluene (60 mL) was added silver carbonate (2.26 g, 8.16 mmol). The reaction mixture was heated at reflux for 3 h. The reaction mixture was then filtered and was concentrated in vacuo. Purification by gradient flash chromatography (methanol/methylene chloride) on a 35 g RediSep disposable column gave (3-benzyloxycarbonylamino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid ethoxycarbonyloxymethyl ester (300 mg, 0.63 mmol). 1H-NMR (CDCl3, 300 MHz): δ 7.35 (m, 5H), 5.65 (m, 2H), 5.45 (br s, 1H), 5.10 (s, 2H), 4.2 (m, 2H), 3.45 (dd, 1H), 3.20 (dd, 1H), 2.01-1.55 (m, 11H), 1.40-0.95 (m, 8H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3 h
  3. filtrationThe reaction mixture was then filtered
  4. concentrationwas concentrated in vacuo
  5. customPurification by gradient flash chromatography (methanol/methylene chloride) on a 35 g RediSep disposable column

Sources & evidence

ORD record
ord-b40d4bac33da4475b895eb569ef6e19d
Source dataset
uspto-grants-2010_03
Patent number
US07687540B2

Reaction notes

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