Sodium borohydride → (2S)-2-(tert-Butoxy)-2-[(20S)-14,16-difluoro-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]acetic acid

HRID 921128Notes

Reaction equation

HRID 921128 reaction equation
[C:1]([O:5][C@@H:6]([C:10]1[C:37]([CH3:38])=[N:36][C:35]2=[CH:39][C:32]3=[N:33][N:34]2[C:11]=1[N:12]1[CH2:44][CH2:43][C:15]([CH3:45])([O:16][CH2:17][CH:18]=[CH:19][CH2:20][C@H:21]([CH3:42])[O:22][C:23]2[C:28]([CH2:29][O:30][CH2:31]3)=[C:27]([F:40])[CH:26]=[C:25]([F:41])[CH:24]=2)[CH2:14][CH2:13]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>C(O)C.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:1]([O:5][C@@H:6]([C:10]1[C:37]([CH3:38])=[N:36][C:35]2=[CH:39][C:32]3=[N:33][N:34]2[C:11]=1[N:12]1[CH2:44][CH2:43][C:15]([CH3:45])([O:16][CH2:17][CH2:18][CH2:19][CH2:20][C@H:21]([CH3:42])[O:22][C:23]2[C:28]([CH2:29][O:30][CH2:31]3)=[C:27]([F:40])[CH:26]=[C:25]([F:41])[CH:24]=2)[CH2:14][CH2:13]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 123222684(2S)-2-(tert-butoxy)-2-[(20S)-14,16-difluoro-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),8,13,15,17,22-octaen-3-yl]acetic acid

Product 1

HCID 118318804(2S)-2-(tert-Butoxy)-2-[(20S)-14,16-difluoro-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]acetic acidYield 19.3%

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 (2S)-2-(tert-butoxy)-2-[(20S)-14,16-difluoro-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),8,13,15,17,22-octaen-3-yl]acetic acid (0.020 g, 0.032 mmol) in ethanol (0.5 mL) were added Hoveyda-Grubbs catalyst 2nd generation (3.99 mg, 6.36 μmol) and sodium borohydride (6.02 mg, 0.159 mmol) and the mixture was stirred at rt. After 30 min, the mixture was quenched with water and the product was extracted with EtOAc. The organic phase was dried (Na2SO4), filtered and concentrated. The crude material was purified via preparative HPLC to afford (2S)-2-(tert-Butoxy)-2-[(20S)-14,16-difluoro-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]acetic acid (3.9 mg, 12.83% yield). 1H NMR (500 MHz, DMSO-d6) δ: 6.92 (d, J=11.7 Hz, 1H), 6.77 (t, J=9.0 Hz, 1H), 6.42 (s, 1H), 4.83-4.54 (m, 4H), 4.49-4.24 (m, 2H), 3.61 (dd, J=10.5, 4.6 Hz, 2H), 3.37 (br. s., 2H), 2.59 (d, J=9.9 Hz, 1H), 2.33-1.97 (m, 4H), 1.93 (br. s., 1H), 1.88-1.41 (m, 9H), 1.31-1.06 (m, 15H). LCMS (M+H) calcd for C33H45F2N4O6: 631.33. found: 631.4.

Workup

  1. customthe mixture was quenched with water
  2. extractionthe product was extracted with EtOAc
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified via preparative HPLC

Sources & evidence

ORD record
ord-2ef71f89bfe24cc986bc16f558fd347d
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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