Water → Methyl(2S)-2-(tert-butoxy)-2-[(22S)-4,5,22,28-tetramethyl-17-(trifluoromethoxy)-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate

HRID 1482089Notes

Reaction equation

HRID 1482089 reaction equation
[CH2:1]([O:4][C:5]1([CH3:55])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:26]5[CH:31]=[C:30]([O:32][C:33]([F:36])([F:35])[F:34])[CH:29]=[CH:28][C:27]=5[O:37][C@H:38]([CH2:40][CH:41]=C)[CH3:39])[CH:23]=[CH:24][CH:25]=4)[N:19]=[C:15]3[C:14]([CH3:43])=[C:13]([CH3:44])[C:12]=2[C@H:45]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])[C:46]([O:48][CH3:49])=[O:47])[CH2:7][CH2:6]1)[CH:2]=C.O.[BH4-].C([N+](CCCC)(CCCC)CCCC)CCC>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(Cl)Cl>[C:51]([O:50][C@@H:45]([C:12]1[C:13]([CH3:44])=[C:14]([CH3:43])[C:15]2=[N:19][C:18]3=[CH:17][N:16]2[C:11]=1[N:8]1[CH2:9][CH2:10][C:5]([CH3:55])([O:4][CH2:1][CH2:2][CH2:41][CH2:40][C@H:38]([CH3:39])[O:37][C:27]2[CH:28]=[CH:29][C:30]([O:32][C:33]([F:34])([F:35])[F:36])=[CH:31][C:26]=2[C:22]2[CH:21]=[C:20]3[CH:25]=[CH:24][CH:23]=2)[CH2:6][CH2:7]1)[C:46]([O:48][CH3:49])=[O:47])([CH3:52])([CH3:53])[CH3:54]

Participants

7

Reactant 3

HCID 962WaterHCID 169536Tetrabutylammonium borohydrideHCID 118308884(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-7,8-dimethyl-2-(2'-((S)-pent-4-en-2-yloxy)-5'-(trifluoromethoxy)-[1,1'-biphenyl]-3-yl)imidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118319893Methyl(2S)-2-(tert-butoxy)-2-[(22S)-4,5,22,28-tetramethyl-17-(trifluoromethoxy)-21,27-dioxa-1,7,34-triazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetateYield 38.3%

Reagents, catalysts & solvents 3

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalystHCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-7,8-dimethyl-2-(2′-((S)-pent-4-en-2-yloxy)-5′-(trifluoromethoxy)-[1,1′-biphenyl]-3-yl)imidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate (0.20 g, 0.262 mmol, 1 equiv) and TsOH monohydrate (50 mg, 0.262 mmol, 1 equiv) in DCE (100 mL) was heated to 80° C. The Hoveyda Grubbs 2nd generation catalyst (16 mg, 0.026 mmol, 0.1 equiv) was added. The pale green brown solution was stirred for 3 h. Upon cooling to ambient temperature, the reaction was washed with saturated aqueous NaHCO3, dried (Na2SO4), and concentrated in vacuo. The crude product was taken up in 20:1 DCE:water (2.8 mL) and tetrabutylammonium borohydride (135 mg, 0.524 mmol, 2 equiv) was added. After 1 h, the reaction mixture was diluted with DCM, washed with water, dried (Na2SO4), and concentrated in vacuo. The crude product was purified by silica gel flash column chromatography (0-100% EtOAc [2% TEA]/hexane) to provide the product (74 mg, 38%) as a tan foam. LCMS (ESI, M+1): 738.80.

Workup

  1. washthe reaction was washed with saturated aqueous NaHCO3
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. waitAfter 1 h
  5. washwashed with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel flash column chromatography (0-100% EtOAc [2% TEA]/hexane)

Sources & evidence

ORD record
ord-7191e3b612b74c6a9d19ea724f0151bc
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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