Ethanol → (2S)-2-(tert-butoxy)-2-{4,26-dimethyl-11,25-dioxa-1,5,7,8-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13(18),14,16-heptaen-3-yl}acetic acid

HRID 921206Notes

Reaction equation

HRID 921206 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:38]([CH3:39])=[N:37][C:36]2=[CH:40][C:33]3=[N:34][N:35]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:25]=[CH:26][CH:27]=[CH:28][C:29]=2[CH2:30][O:31][CH2:32]3)[CH2:16][CH2:15]1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[CH3:46]CO>>[C:1]([O:5][C@@H:6]([C:12]1[C:38]([CH3:39])=[N:37][C:36]2=[CH:40][C:33]3=[N:34][N:35]2[C:13]=1[N:14]1[CH2:15][CH2:16][C:17]([CH3:43])([O:18][CH2:19][CH2:20][CH2:46][CH2:21][CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=2[CH2:30][O:31][CH2:32]3)[CH2:41][CH2:42]1)[C:7]([OH:9])=[O:8])([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 118318855ethyl (2S)-2-(tert-butoxy)-2-{4,25-dimethyl-11,24-dioxa-1,5,7,8-tetraazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetate

Product 1

HCID 118318860(2S)-2-(tert-butoxy)-2-{4,26-dimethyl-11,25-dioxa-1,5,7,8-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13(18),14,16-heptaen-3-yl}acetic acidYield 59.6%

Procedure

A mixture of ethyl (2S)-2-(tert-butoxy)-2-{4,25-dimethyl-11,24-dioxa-1,5,7,8-tetraazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetate (37 mg, 0.062 mmol) and NaOH (0.312 mL, 0.312 mmol) in EtOH (2 mL) was refluxed for 2 h. It was then filtered and purified by preparative HPLC to obtain (2S)-2-(tert-butoxy)-2-{4,26-dimethyl-11,25-dioxa-1,5,7,8-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13(18),14,16-heptaen-3-yl}acetic acid (21 mg, 0.037 mmol, 59.6% yield) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.29 (d, J=7.7 Hz, 1H), 7.26-7.19 (m, 2H), 7.17-7.11 (m, 1H), 6.53 (s, 1H), 5.71 (s, 1H), 4.74-4.58 (m, 4H), 4.50-4.42 (m, 1H), 3.68-3.20 (m, 4H), 2.82-2.75 (m, 1H), 2.66 (d, J=8.4 Hz, 2H), 2.51 (s, 3H), 1.90-1.81 (m, 2H), 1.71-1.51 (m, 8H), 1.19 (s, 3H), 1.15 (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-9d588d29204440569de53c01aa21f569
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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