Sodium Hydroxide → (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]acetic acid

HRID 921118Notes

Reaction equation

HRID 921118 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][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)[CH2:16][CH2:15]1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[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]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 118318800HCID 118318800, compound

Product 1

HCID 118318801(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]acetic acidYield 12%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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),8,13,15,17-heptaen-3-yl]acetate (36.5 mg, 0.057 mmol) in Methanol (3 mL) was added sodium hydroxide/1N (0.285 mL, 0.285 mmol) and the resulting solution was refluxed. After 3 h, The mixture was cooled and concentrated. The residue was purified by prep HPLC to afford (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]acetic acid (4.2 mg, 11.31% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.96 (s, 1H), 7.13 (dd, J=9.0, 2.8 Hz, 1H), 7.06-6.89 (m, 2H), 6.49 (s, 1H), 5.57 (s, 1H), 4.87 (d, J=12.5 Hz, 1H), 4.69-4.45 (m, 4H), 4.32 (t, J=11.6 Hz, 1H), 3.70-3.19 (m, 5H), 2.80 (br. s., 1H), 2.49-2.44 (m, 3H), 1.88 (d, J=14.3 Hz, 2H), 1.74-1.46 (m, 8H), 1.22-1.05 (m, 15H).

Workup

  1. temperaturethe resulting solution was refluxed
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated
  4. customThe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-0d7d2d57273946c986a65d23b4a31752
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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