Ozone → [1-(Acetylaminomethyl)-2-methylcarbamoyl-2-oxoethyl]carbamic acid benzyl ester

HRID 1861828Notes

Reaction equation

HRID 1861828 reaction equation
[CH2:1]([O:8][C:9](=[O:41])[NH:10][CH:11]([CH2:36][NH:37][C:38](=[O:40])[CH3:39])[C:12](=[O:35])[C:13](C#N)=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:42]=[O+][O-].CC[N:47]([CH:51](C)C)C(C)C.Cl.CN>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:41])[NH:10][CH:11]([CH2:36][NH:37][C:38](=[O:40])[CH3:39])[C:12]([C:13](=[O:42])[NH:47][CH3:51])=[O:35])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 24823OzoneHCID 81531Diisopropylethylamine2×HCID 6364545Methylamine hydrochloride2×HCID 86758881[1-(Acetylaminomethyl)-3-cyano-2-oxo-3-(triphenyl-lambda5-phosphanylidene) propyl]carbamic acid benzyl ester

Product 1

HCID 69905615[1-(Acetylaminomethyl)-2-methylcarbamoyl-2-oxoethyl]carbamic acid benzyl esterYield 17%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of [1-(acetylaminomethyl)-3-cyano-2-oxo-3-(triphenyl-λ5-phosphanylidene) propyl]carbamic acid benzyl ester (569.9 mg, 1.01 mmol, 1 equiv) in CH2Cl2 (11 mL) at −78° C. was treated with ozone gas for 3 h. The chilled solution was then purged with Ar for 30 min until the color had changed from green to yellow. DIEA (0.211 mL, 1.21 mmol, 1.2 equiv) and methylamine hydrochloride (75.1 mg, 1.11 mmol, 1.1 equiv) were added. After 1.5 h at −78° C., a second portion of DIEA (0.25 mL, 1.43 mmol, 1.4 equiv) and methylamine hydrochloride (80.0 mg, 1.18 mmol, 1.17 equiv) were added, and stirring continued at −78° C. for 2.5 h longer. The volatiles were removed under reduced pressure, and the residue was purified by flash column chromatography (5% CH3OH in CH2Cl2) to give [1-(acetylaminomethyl)-2-methylcarbamoyl-2-oxoethyl]carbamic acid benzyl ester (55.8 mg, 17% yield) as a pale yellow solid. Rf=0.23 (10% CH3OH in CH2Cl2). IR (cm−1) 3302, 1709, 1658, 1539. 1H NMR (CDCl3) (rotameric mixture) δ1.89, 1.95 (2 s, 3H), 2.77 and 2.89 (2 d, 3H, J =5.2), 3.47-3.54 (m, 1H), 3.61-3.69 (m, 1H), 4.29 (m, 1H), 5.10 (s, 2H), 6.64 (br s, 1H), 6.85 (br s, 1H), 7.06 (br s, 1H), 7.34 (s, 5H).

Workup

  1. customThe chilled solution was then purged with Ar for 30 min until the color
  2. waitcontinued at −78° C. for 2.5 h
  3. customThe volatiles were removed under reduced pressure
  4. customthe residue was purified by flash column chromatography (5% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-74a5672f854e4167aa26b6816adf7e6e
Source dataset
uspto-grants-2003_03
Patent number
US06534530B1

Reaction notes

Loading…