4-Methylmorpholine → HCID 131720975, compound

HRID 1457239Notes

Reaction equation

HRID 1457239 reaction equation
[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3](C3)[CH:2]1[O:11][C:12]([NH:14][C@H:15]([C:26](O)=[O:27])[CH2:16][C:17]1[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][CH:18]=1)=[O:13])[CH2:8]2.[CH3:29][N:30]1CCOCC1.[C:36](=[O:38])=O.[CH2:39](O)C1C=CC=CC=1.C(OC(Cl)=O)C(C)C.Cl.CNOC>ClCCl>[NH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([CH2:16][C@@H:15]([NH:14][C:12](=[O:13])[O:11][CH:2]([CH2:3][CH2:9][CH2:7][CH2:8][CH2:1][CH2:10][CH2:5][CH3:6])[CH3:39])[C:26]([NH:30][CH2:29][O:38][CH3:36])=[O:27])=[CH:18]1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 53956425HCID 53956425, compoundHCID 131720976HCID 131720976, compound

Product 1

HCID 131720975HCID 131720975, compoundYield 730%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of acid (1) (859 mg, 2.25 mmol) in dichloromethane (8 mL) was added N-methylmorpholine (495 μL, 4.50 mmol). The mixture was cooled to -15° C. (CO2 /benzyl alcohol) and isobutylchloroformate (292 μL, 2.25 mmol) was added. The mixture was stirred at -15° C for 15 minutes followed by the addition of N,O-dimethylhydroxylamine hydrochloride (219 mg, 2.25 mmol). The reaction mixture was stirred at -15° C. for 1 hour, then warmed to room temperature and stirred for a further 15 hours. The mixture was filtered and the filtrate washed sequentially with sodium hydrogen carbonate, water, 10% citric acid and brine, dried (MgSO4) and evaporated to dryness. The crude material was purified by column chromatography to give hydroxamate (2) (694 mg, 730%) as a white foam; m.p. 72°-80° C. (Found: C, 67.4; H, 7.35; N, 9.8%. C24H31N3O4 requires C, 67.7; H, 7.3; N, 9.9%); [α]20 =-9.4° (C=0.3, CHCl3); (S-ISOMER) [α]20 =+8.9° (C=0.3, CHCl3)); υmax (film); 1 695 (CO urethane), 1 657 (CO amide) 741 cm-1 (disubstituted Ph); H (CHCl3), δ6 1.30-2.01 (14H, m, adamantyl), 2.99-3.24 (5H, m, indole CH2 +NCH3), 3.58 (3H, s, OCH3), 4.7 (1H, s, adamantyl 2-H), 5.00 (1H, br d, CH (NHR)CON-), 5.36 (1H br d, urethane NH), 6.92-7.17 (3H, m, indole 2,5,6-H), 7.27 (1H, d, J 8 Hz, indole 7-H), 7.53 (1H, d, J 8 Hz, indole 4-H), 7.99 (1H, s, indole NH).

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at -15° C. for 1 hour
  3. temperaturewarmed to room temperature
  4. stirringstirred for a further 15 hours
  5. filtrationThe mixture was filtered
  6. washthe filtrate washed sequentially with sodium hydrogen carbonate, water, 10% citric acid and brine
  7. dry with materialdried (MgSO4)
  8. customevaporated to dryness
  9. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-de9030d99122444d9b569146fffce5ec
Source dataset
uspto-grants-1998_12
Patent number
US05846942

Reaction notes

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