Ethyl acetate hexane → Methyl (2S)-2-(tert-butoxy)-2-[(23Z)-4,27-dimethyl-26-oxa-1,5,7,8-tetraazahexacyclo[25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-yl]acetate

HRID 1400728Notes

Reaction equation

HRID 1400728 reaction equation
C([O:4][C:5]1([CH3:47])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:26]5C=[CH:30][CH:29]=[CH:28][C:27]=5CCC=C)[CH:23]=[CH:24][CH:25]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:36])[C:12]=2[C@H:37]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C:38]([O:40][CH3:41])=[O:39])[CH2:7][CH2:6]1)C=C.[CH3:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53].CCOC(C)=O>ClCCCl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[C:43]([O:42][C@@H:37]([C:12]1[C:13]([CH3:36])=[N:14][C:15]2=[CH:19][C:18]3=[N:17][N:16]2[C:11]=1[N:8]1[CH2:9][CH2:10][C:5]([CH3:47])([O:4][CH2:48][CH:49]=[CH:50][CH2:51][CH2:52][C:53]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:22]2[CH:21]=[C:20]3[CH:25]=[CH:24][CH:23]=2)[CH2:6][CH2:7]1)[C:38]([O:40][CH3:41])=[O:39])([CH3:46])([CH3:44])[CH3:45]

Participants

5

Reactant 2

HCID 21226206Ethyl acetate hexaneHCID 86710778(S)-methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(2'-(but-3-en-1-yl)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 86710781Methyl (2S)-2-(tert-butoxy)-2-[(23Z)-4,27-dimethyl-26-oxa-1,5,7,8-tetraazahexacyclo[25.2.2.16,9.110,14.02,7.015,20]tritriaconta-2,4,6(33),8,10(32),11,13,15(20),16,18,23-undecaen-3-yl]acetate

Reagents, catalysts & solvents 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
75 °C

Procedure

(S)-Methyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(2′-(but-3-en-1-yl)-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (116 mg, 0.182 mmol) was dissolved in DCE (150 mL). The solution was heated to 75° C. in an oil bath under an N2 atmosphere. Once the reaction flask had reached 75° C. the Hoveyda-Grubbs Catalyst 2nd generation (11.45 mg, 0.018 mmol) was added. The yellow reaction mixture turned green. Stirring at 85° C. was continued for 2 h at which time the reaction appeared complete by TLC (4:1 hexane/EtOAc) and HPLC (˜4:1 mixture of E/Z isomers). The cooled reaction mixture was concentrated in vacuo and purified by Biotage chromatography (0-50% EtOAc/hexanes) to give 84 mg of the desired product as a colorless oil. LCMS (M+H).=609.

Workup

  1. customhad reached 75° C.
  2. additionwas added
  3. customThe cooled reaction mixture
  4. concentrationwas concentrated in vacuo
  5. custompurified by Biotage chromatography (0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b8a01dabf7a443f583779a6f7e785506
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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