Ammonia hydroxide → (5)-Tert-butyl 21-amino-2,2-dimethyl-4,18-dioxo-3,8,11,14-tetraoxa-5,17-diazadocosan-22-oate

HRID 530144Notes

Reaction equation

HRID 530144 reaction equation
C1C2C(COC(=O)[NH:17][C@H:18]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:19][CH2:20][C:21](=[O:42])[NH:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])C3C(=CC=CC=3)C=2C=CC=1.[OH-].N>O1CCOCC1>[NH2:17][C@H:18]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:19][CH2:20][C:21](=[O:42])[NH:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:38])([CH3:39])[CH3:40]

Participants

4

Reactant 2

HCID 21862953Ammonia hydroxideHCID 90418350(S)-tert-butyl 1-(9H-fluoren-9-yl)-24,24-dimethyl-3,8,22-trioxo-2,12,15,18,23-pentaoxa-4,9,21-triazapentacosane-5-carboxylate

Product 1

HCID 90418780(5)-Tert-butyl 21-amino-2,2-dimethyl-4,18-dioxo-3,8,11,14-tetraoxa-5,17-diazadocosan-22-oateYield 99.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To (S)-tert-butyl 1-(9H-fluoren-9-yl)-24,24-dimethyl-3,8,22-trioxo-2,12,15,18,23-pentaoxa-4,9,21-triazapentacosane-5-carboxylate (1.18 g, 1.69 mmol), in 1,4-dioxane (45 mL) chilled to 0° C. concentrated ammonia hydroxide (9.5 mL, 133 mmol) was added dropwise over 15 minutes. The reaction was stirred at 0° C. for 2 hours and then at ambient temperature for 16 hours. After this time, the reaction was dry loaded onto silica and purified by silica gel column chromatography eluting with methylene chloride to 3:17 methanol/methylene chloride to afford (S)-tert-butyl 21-amino-2,2-dimethyl-4,18-dioxo-3,8,11,14-tetraoxa-5,17-diazadocosan-22-oate (802 mg, 99%) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 6.92 (bs, 1H), 5.14 (bs, 3H), 3.90-3.85 (m, 1H), 3.80-3.54 (m, 9H), 3.49-3.45 (m, 2H), 3.34-3.29 (m, 2H), 3.23-3.15 (m, 3H), 2.61-2.41 (m, 2H), 2.33-2.23 (m, 1H), 2.15-2.03 (m, 1H), 1.48 (s, 9H), 1.46 (s, 9H); ESI MS m/z=478 [M+H]+.

Workup

  1. additionwas added dropwise over 15 minutes
  2. waitat ambient temperature for 16 hours
  3. customAfter this time, the reaction was dry
  4. custompurified by silica gel column chromatography
  5. washeluting with methylene chloride to 3:17 methanol/methylene chloride

Sources & evidence

ORD record
ord-7a7c8cc52fea4159871b6c27a9dd7ebb
Source dataset
uspto-grants-2016_05
Patent number
US09352049B2

Reaction notes

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