Sodium Hydroxide → HCID 118318891, compound

HRID 921253Notes

Reaction equation

HRID 921253 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:37]([CH3:38])=[N:36][C:35]2=[CH:39][C:32]3=[N:33][N:34]2[C:13]=1[N:14]1[CH2:43][CH2:42][C:17]([CH3:44])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[CH:24]=[C:25]([F:41])[C:26]([F:40])=[CH:27][C:28]=2[CH2:29][O:30][CH2:31]3)[CH2:16][CH2:15]1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CCO>[C:1]([O:5][C@@H:6]([C:12]1[C:37]([CH3:38])=[N:36][C:35]2=[CH:39][C:32]3=[N:33][N:34]2[C:13]=1[N:14]1[CH2:43][CH2:42][C:17]([CH3:44])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[CH:24]=[C:25]([F:41])[C:26]([F:40])=[CH:27][C:28]=2[CH2:29][O:30][CH2:31]3)[CH2:16][CH2:15]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 118318892HCID 118318892, compound

Product 1

HCID 118318891HCID 118318891, compoundYield 56.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of ethyl (2S)-2-(tert-butoxy)-2-{15,16-difluoro-4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16-heptaen-3-yl}acetate (60 mg, 0.098 mmol) and NaOH (3.90 mg, 0.098 mmol) in EtOH (2 mL) was refluxed for 2 h. It was then cooled to rt and purified by preparative HPLC to isolate (2S)-2-(tert-butoxy)-2-{15,16-difluoro-4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16-heptaen-3-yl}acetic acid (32.5 mg, 55.6%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.44-7.31 (m, 1H), 7.27 (dd, J=11.6, 8.6 Hz, 1H), 6.51 (s, 1H), 5.71 (s, 1H), 4.97-4.76 (m, 3H), 4.62 (d, J=12.5 Hz, 1H), 4.49 (t, J=11.2 Hz, 1H), 3.63-3.53 (m, 2H), 3.21-3.19 (m, 2H), 2.68-2.56 (m, 3H), 2.50 (br. s., 3H), 1.83 (d, J=12.8 Hz, 3H), 1.71-1.50 (m, 5H), 1.18 (s, 3H), 1.15 (s, 9H). LCMS (M+1)=587.3.

Workup

  1. temperaturewas refluxed for 2 h
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-a1107a81db804f7cbb3e8bd171061c42
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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