Sodium Hydroxide → (2S)-2-(tert-butoxy)-2-{4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.113,17.02,7]triaconta-2,4,6(30),8,13(29),14,16-heptaen-3-yl}acetic acid

HRID 921212Notes

Reaction equation

HRID 921212 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[CH2:42][CH2:41][C:17]([CH3:43])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]2[CH:40]=[C:28]([CH2:29][O:30][CH2:31]3)[CH:27]=[CH:26][CH:25]=2)[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[CH2:15][CH2:16][C:17]([CH3:43])([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]2[CH:40]=[C:28]([CH2:29][O:30][CH2:31]3)[CH:27]=[CH:26][CH:25]=2)[CH2:41][CH2:42]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 118318863ethyl (2S)-2-(tert-butoxy)-2-{4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.113,17.02,7]triaconta-2,4,6(30),8,13(29),14,16-heptaen-3-yl}acetate

Product 1

HCID 118318864(2S)-2-(tert-butoxy)-2-{4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.113,17.02,7]triaconta-2,4,6(30),8,13(29),14,16-heptaen-3-yl}acetic acidYield 51.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of ethyl (2S)-2-(tert-butoxy)-2-{4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.113,17.02,7]triaconta-2,4,6(30),8,13(29),14,16-heptaen-3-yl}acetate (20 mg, 0.034 mmol) and NaOH (0.169 mL, 0.169 mmol) in EtOH (2 mL) was refluxed for 2 h. It was then filtered and purified by preparative HPLC to isolate (2S)-2-(tert-butoxy)-2-{4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.113,17.02,7]triaconta-2,4,6(30),8,13(29),14,16-heptaen-3-yl}acetic acid (10 mg, 0.017 mmol, 51.4% yield) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.34-7.27 (m, 1H), 7.22 (s, 1H), 7.16 (d, J=7.3 Hz, 2H), 6.50 (s, 1H), 5.62 (s, 1H), 4.62-4.40 (m, 4H), 4.17 (t, J=12.5 Hz, 1H), 3.65-3.56 (m, 1H), 3.38-3.23 (m, 2H), 2.77 (d, J=11.4 Hz, 1H), 2.74-2.66 (m, 1H), 2.59-2.53 (m, 1H), 2.50 (br. s., 4H), 1.91 (d, J=12.5 Hz, 1H), 1.84-1.75 (m, 1H), 1.75-1.62 (m, 3H), 1.58-1.44 (m, 3H), 1.43-1.33 (m, 2H), 1.17 (s, 3H), 1.14 (s, 9H). LCMS (M+1)=565.3.

Workup

  1. temperaturewas refluxed for 2 h
  2. filtrationIt was then filtered
  3. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-ca532649a0a54cc7bb7567fbd68fd465
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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