4-Methylmorpholine → 2,2-Dimethyl-propanoic Acid [3-Chloro-2-[[[2-[(triphenylmethyl)amino]-5-thiazolyl]carbonyl]amino]phenyl]methyl Ester

HRID 1437118Notes

Reaction equation

HRID 1437118 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][OH:9])[C:3]=1[NH:10][C:11]([C:13]1[S:17][C:16]([NH:18][C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:15][CH:14]=1)=[O:12].CN1CCOCC1.[CH3:45][C:46]([CH3:51])([CH3:50])[C:47](Cl)=[O:48].[NH4+].[Cl-]>C1COCC1.O>[C:47]([O:9][CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[NH:10][C:11]([C:13]1[S:17][C:16]([NH:18][C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:15][CH:14]=1)=[O:12])(=[O:48])[C:46]([CH3:51])([CH3:50])[CH3:45]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 25517Ammonium ChlorideHCID 62493Pivaloyl chlorideHCID 25022845HCID 25022845, compound

Product 1

HCID 250228462,2-Dimethyl-propanoic Acid [3-Chloro-2-[[[2-[(triphenylmethyl)amino]-5-thiazolyl]carbonyl]amino]phenyl]methyl EsterYield 104.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound 7a (7.36 g, 14 mmol) in THF (200 mL) at 5° C. were added N-methylmorpholine (3.1 mL, 28 mmol) followed by slow addition of trimethylacetyl chloride (8a, 1.8 mL, 21 mmol). The reaction mixture was allowed to warm to room temperature over a period of 3 h. A solution of saturated NH4Cl in H2O (500 mL) was added. The mixture was extracted with EtOAc (2×250 mL). The combined extracts were washed with 1N HCl (500 mL), saturated NaHCO3 (500 mL), dried over MgSO4. The solution was filtered and concentrated in vacuo to give compound 9a as a white solid (8.90 g, 100% yield). 1H NMR (500 MHz, CDCl3) δ 1.16 (s, 9H), 5.01 (s, 2H), 7.20-7.40 (m, 18H), 7.79 (s, 1H), 8.30 (bs, 1H).

Workup

  1. extractionThe mixture was extracted with EtOAc (2×250 mL)
  2. washThe combined extracts were washed with 1N HCl (500 mL), saturated NaHCO3 (500 mL)
  3. dry with materialdried over MgSO4
  4. filtrationThe solution was filtered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e69b4ec8ff90492fbfb9724f14487845
Source dataset
uspto-grants-2009_11
Patent number
US07622473B2

Reaction notes

Loading…