Sodium borohydride → HCID 118318800, compound

HRID 921117Notes

Reaction equation

HRID 921117 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:39]([CH3:40])=[N:38][C:37]2=[CH:41][C:34]3=[N:35][N:36]2[C:13]=1[N:14]1[CH2:45][CH2:44][C:17]([CH3:46])([O:18][CH2:19][CH:20]=[CH:21][CH2:22][C@H:23]([CH3:43])[O:24][C:25]2[CH:26]=[CH:27][C:28]([F:42])=[CH:29][C:30]=2[CH2:31][O:32][CH2:33]3)[CH2:16][CH2:15]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>C(O)C.C1(C)C=C(C)C=C(C)C=1N1CCN(C2C(C)=CC(C)=CC=2C)C1=[Ru](Cl)(Cl)=CC1C=CC=CC=1OC(C)C>[C:1]([O:5][C@@H:6]([C:12]1[C:39]([CH3:40])=[N:38][C:37]2=[CH:41][C:34]3=[N:35][N:36]2[C:13]=1[N:14]1[CH2:15][CH2:16][C:17]([CH3:46])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][C@H:23]([CH3:43])[O:24][C:25]2[C:30]([CH2:31][O:32][CH2:33]3)=[CH:29][C:28]([F:42])=[CH:27][CH:26]=2)[CH2:44][CH2:45]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 123202498HCID 123202498, compound

Product 1

HCID 118318800HCID 118318800, compoundYield 79%

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 702EthanolSolvent

Procedure

To a solution of ethyl (2S)-2-(tert-butoxy)-2-[(20S)-15-fluoro-4,20,26-trimethyl-11,19,25-trioxa-1,5,7,8-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13(18),14,16,22-octaen-3-yl]acetate: (46.1 mg, 0.072 mmol) in ethanol (3 mL) were added (1,3-dimesitylimidazolidin-2-ylidene)(2-isopropoxybenzylidene)ruthenium(VI) chloride (9.04 mg, 0.014 mmol) then sodium borohydride (13.65 mg, 0.361 mmol) and the mixture was stirred at rt. After 10 min, LCMS indicated completion of reaction. The reaction was quenched with water and extracted with EtOAc. The organic phase was dried (Na2SO4), filtered and concentrated. The crude was purified by flash chromatography (Biotage; 0%-100% EtOAc/hexane; 20 CV) to give ethyl (2S)-2-(tert-butoxy)-2-[(20S)-15-fluoro-4,20,26-trimethyl-11,19,25-trioxa-1,5,7,8-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13,15,17-heptaen-3-yl]acetate (36.5 mg, 0.057 mmol, 79% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ δ 7.15 (dd, J=9.0, 3.2 Hz, 1H), 6.89 (td, J=8.6, 3.2 Hz, 1H), 6.79 (dd, J=8.9, 4.5 Hz, 1H), 6.56 (s, 1H), 5.97 (s, 1H), 4.93 (d, J=12.2 Hz, 1H), 4.75-4.66 (m, 3H), 4.56-4.39 (m, 2H), 4.29-4.15 (m, 2H), 3.97-3.81 (m, 1H), 3.56-3.34 (m, 2H), 3.14 (d, J=11.7 Hz, 1H), 2.83 (d, J=12.2 Hz, 1H), 2.61 (s, 3H), 2.03-1.53 (m, 10H), 1.34-1.13 (m, 18H). LCMS (M+H) calcd for C35H50FN4O6: 641.37. found: 641.6.

Workup

  1. customcompletion of reaction
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified by flash chromatography (Biotage; 0%-100% EtOAc/hexane; 20 CV)

Sources & evidence

ORD record
ord-e0645610e54748be90baba6a3808ff1f
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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