1,2-Dichloroethane → [1-(Acetylaminomethyl)-3-cyano-2-oxo-3-(triphenyl-lambda5-phosphanylidene) propyl]carbamic acid benzyl ester

HRID 1861827Notes

Reaction equation

HRID 1861827 reaction equation
[C:1]([NH:4][CH2:5][CH:6]([NH:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[C:7]([OH:9])=O)(=[O:3])[CH3:2].C(Cl)CCl.[C:25]([CH:27]=[P:28]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)#[N:26]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:14]([O:13][C:11](=[O:12])[NH:10][CH:6]([CH2:5][NH:4][C:1](=[O:3])[CH3:2])[C:7](=[O:9])[C:27]([C:25]#[N:26])=[P:28]([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 85524(Triphenylphosphoranylidene)acetonitrileHCID 186216323-Acetylamino-2-benzyloxycarbonylaminopropionic acid

Product 1

HCID 86758881[1-(Acetylaminomethyl)-3-cyano-2-oxo-3-(triphenyl-lambda5-phosphanylidene) propyl]carbamic acid benzyl esterYield 70.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

This intermediate was prepared generally according to the method of Wasserman et al., J. Org. Chem. (1994), vol. 59, 4364. In particular, to a solution of (3-acetylamino-2-benzyloxycarbonylaminopropionic acid (1.40 g, 5.0 mmol, 1 equiv) in CH2Cl2 (50 mL) at 0° C. were added EDC (1.00 g, 5.25 mmol, 1.05 equiv) and DMAP (61 mg, 0.5 mmol, 0.1 equiv). A solution of (cyanomethylene)triphenylphosphorane (prepared as described in Freudenreich et al., J. Am. Chem. Soc. (1984), vol. 106, 3344) (2.50 g, 8.30 mmol, 1.66 equiv) in CH2Cl2 (16 mL) was added to the acid solution dropwise over 20 min. After stirring 2 h at 0° C., the reaction mixture was partitioned between deionized water (30 mL) and CH2Cl2 (3×50 mL). The combined organic layers were washed with brine (30 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by flash column chromatography (5% CH3OH in CH2Cl2) to give [1-(acetylaminomethyl)-3-cyano-2-oxo-3-(triphenyl-λ5-phosphanylidene)propyl]-carbamic acid benzyl ester (1.98 g, 70% yield) as a colorless foam. Rf=0.40 (10% CH3OH in CH2Cl2). IR (cm−1) 3312, 2175, 1716, 1437. 1H NMR (CDCl3) δ1.91 (s, 3H), 3.66-3.79 (m, 2H), 5.04-5.06 (m, 1H), 5.10 (s, 2H), 5.94 (br s, 1H), 6.21 (br s, 1H), 7.26-7.70 (m, 21H).

Workup

  1. customThis intermediate was prepared generally
  2. customthe reaction mixture was partitioned between deionized water (30 mL) and CH2Cl2 (3×50 mL)
  3. washThe combined organic layers were washed with brine (30 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography (5% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-093d3124310748978e1c439bbe2bee4b
Source dataset
uspto-grants-2003_03
Patent number
US06534530B1

Reaction notes

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