Sodium borohydride → (2S)-2-(tert-butoxy)-2-[(20S)-4,15,20,26-tetramethyl-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 921123Notes

Reaction equation

HRID 921123 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[CH2:43][CH2:42][C:15]([CH3:44])([O:16][CH2:17][CH:18]=[CH:19][CH2:20][C@H:21]([CH3:41])[O:22][C:23]2[C:28]([CH2:29][O:30][CH2:31]3)=[CH:27][C:26]([CH3:40])=[CH:25][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[CH2:13][CH2:14][C:15]([CH3:44])([O:16][CH2:17][CH2:18][CH2:19][CH2:20][C@H:21]([CH3:41])[O:22][C:23]2[C:28]([CH2:29][O:30][CH2:31]3)=[CH:27][C:26]([CH3:40])=[CH:25][CH:24]=2)[CH2:42][CH2:43]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 123933559(2S)-2-(tert-butoxy)-2-[(20S)-4,15,20,26-tetramethyl-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 118318802(2S)-2-(tert-butoxy)-2-[(20S)-4,15,20,26-tetramethyl-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 10.5%

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)-4,15,20,26-tetramethyl-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, 0.033 mmol) in ethanol (1 mL) was added Hoveyda-Grubbs catalyst 2nd generation (4.13 mg, 6.59 μmol). Sodium borohydride (6.24 mg, 0.165 mmol) was added and the mixture was stirred at rt. After 45 min, the reaction was quenched by careful addition of water. The product was extracted with EtOAc, dried (Na2SO4), filtered and concentrated. The crude material was purified via preparative HPLC to afford (2S)-2-(tert-butoxy)-2-[(20S)-4,15,20,26-tetramethyl-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 (2.1 mg, 9.94% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.14 (s, 1H), 7.04-6.95 (m, 1H), 6.86 (d, J=8.4 Hz, 1H), 6.42 (s, 1H), 4.83 (d, J=12.5 Hz, 1H), 4.62-4.42 (m, 3H), 4.39-4.26 (m, 1H), 3.47-3.31 (m, 3H), 2.85-2.74 (m, 1H), 2.64 (br. s., 1H), 2.42-2.33 (m, 1H), 2.23 (s, 3H), 2.02-1.30 (m, 14H), 1.28-0.96 (m, 15H). LCMS (M+H) calcd for C34H49N4O6: 609.36. found: 609.4.

Workup

  1. customthe reaction was quenched by careful addition of water
  2. extractionThe product was extracted with EtOAc
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified via preparative HPLC

Sources & evidence

ORD record
ord-c1e3cab0d81b43b8ab2974f5b107641e
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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