(S)-2-(2-Allyloxy-benzoylamino)-3-(4-allyloxy-3-chloro-phenyl)-propionic acid methyl ester → (E)-(S)-19-Chloro-5-oxo-12,17-dioxa-4-aza-tricyclo[16.2.2.0*6,11*]docosa-1(21),6,8,10,14,18(22),19-heptaene-3-carboxylic acid methyl ester

HRID 928223Notes

Reaction equation

HRID 928223 reaction equation
[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:17][C:18](=[O:29])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[O:25][CH2:26]C=C)[C:13]([O:15][CH3:16])=[O:14])=[CH:7][C:6]=1[Cl:30])[CH:2]=[CH2:3]>Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1.C(Cl)Cl>[CH3:16][O:15][C:13]([C@H:12]1[NH:17][C:18](=[O:29])[C:19]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[O:25][CH2:26][CH:3]=[CH:2][CH2:1][O:4][C:5]2=[CH:10][CH:9]=[C:8]([CH:7]=[C:6]2[Cl:30])[CH2:11]1)=[O:14]

Participants

4

Reactant 1

HCID 86691118(S)-2-(2-Allyloxy-benzoylamino)-3-(4-allyloxy-3-chloro-phenyl)-propionic acid methyl ester

Product 1

HCID 89701942(E)-(S)-19-Chloro-5-oxo-12,17-dioxa-4-aza-tricyclo[16.2.2.0*6,11*]docosa-1(21),6,8,10,14,18(22),19-heptaene-3-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 178425456HCID 178425456, compoundCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

In a 250 mL three-necked flask, Grubbs II catalyst (56.3 mg, 66.3 μmol, Eq: 0.30) was combined with dry DCM (50 mL) to give a brown solution. The reaction mixture was heated to 50° C. (reflux) under argon atmosphere. (S)-methyl 3-(4-(allyloxy)-3-chlorophenyl)-2-(2-(allyloxy)benzamido)propanoate (95 mg, 221 μmol, Eq: 1.00) dissolved in dry DCM (30 mL) was added dropwise. The reaction mixture was stirred at 50° C. for 2 h under argon atmosphere. The reaction mixture was stirred for 1 h at 50° C. to drive the reaction to completion. The crude reaction mixture was concentrated in vacuo and purified by flash chromatography (silica gel, 10 g, n-heptane/AcOEt 4/1, 3/1) to yield a brown oil (42 mg; 47%). m/z=402.2 [M+H]+.

Workup

  1. customto give a brown solution
  2. temperature(reflux) under argon atmosphere
  3. additionwas added dropwise
  4. stirringThe reaction mixture was stirred for 1 h at 50° C.
  5. customthe reaction to completion
  6. customThe crude reaction mixture
  7. concentrationwas concentrated in vacuo
  8. custompurified by flash chromatography (silica gel, 10 g, n-heptane/AcOEt 4/1, 3/1)
  9. customto yield a brown oil (42 mg; 47%)

Sources & evidence

ORD record
ord-6275114a18d745378b10a9850eb51198
Source dataset
uspto-grants-2016_03
Patent number
US09290467B2

Reaction notes

Loading…