Sodium borohydride → (2S)-2-(tert-butoxy)-2-[(20S)-16-chloro-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 921135Notes

Reaction equation

HRID 921135 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][CH:26]=[C:25]([Cl:40])[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][CH:26]=[C:25]([Cl:40])[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 123765054(2S)-2-(tert-butoxy)-2-[(20S)-16-chloro-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 118318810(2S)-2-(tert-butoxy)-2-[(20S)-16-chloro-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 30.4%

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)-16-chloro-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 (1 mL) was added Hoveyda-Grubbs catalyst 2nd generation (4.00 mg, 6.38 μmol). Sodium borohydride (6.03 mg, 0.159 mmol) was added and the mixture was stirred at rt. After 30 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)-16-chloro-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 (6.1 mg, 9.70 μmol, 30.4% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.32 (d, J=8.1 Hz, 1H), 7.06 (s, 1H), 6.94 (d, J=8.1 Hz, 1H), 6.48 (s, 1H), 5.63 (br. S., 1H), 4.84 (d, J=12.5 Hz, 1H), 4.69-4.48 (m, 4H), 4.32 (t, J=11.9 Hz, 1H), 3.65 (br. S., 1H), 3.35-3.22 (m, 4H), 2.74 (s, 3H), 2.02-1.40 (m, 10H), 1.26-0.95 (m, 15H). LCMS (M+H) calcd for C33H46ClN4O6: 629.31. found: 629.4.

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-5a7f353a56ab4f56a356fae57eb6dea4
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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