1,1,3,3-Tetramethylguanidine → Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(5-(4-(heptyloxy)phenyl) thiazol-2-yl)phenyl)acrylate

HRID 716405Notes

Reaction equation

HRID 716405 reaction equation
CN(C)C(N(C)C)=N.[CH2:9]([O:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[S:27][C:26]([C:28]3[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=3)=[N:25][CH:24]=2)=[CH:19][CH:18]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].[C:36]([O:40][C:41]([NH:43][CH:44](P(OC)(OC)=O)[C:45]([O:47][CH3:48])=[O:46])=[O:42])([CH3:39])([CH3:38])[CH3:37]>C1COCC1.C(Cl)Cl>[C:36]([O:40][C:41]([NH:43][C:44](=[CH:32][C:31]1[CH:30]=[CH:29][C:28]([C:26]2[S:27][C:23]([C:20]3[CH:21]=[CH:22][C:17]([O:16][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[CH:18][CH:19]=3)=[CH:24][N:25]=2)=[CH:35][CH:34]=1)[C:45]([O:47][CH3:48])=[O:46])=[O:42])([CH3:37])([CH3:38])[CH3:39]

Participants

6

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 397380Methyl ((tert-butoxy(hydroxy)methylidene)amino)(dimethoxyphosphoryl)acetateHCID 866896684-(5-(4-(Heptyloxy)phenyl)thiazol-2-yl)benzaldehyde

Product 1

HCID 89619578Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(5-(4-(heptyloxy)phenyl) thiazol-2-yl)phenyl)acrylateYield 83.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

A stirring mixture of 1,1,3,3-tetramethylguanidine (86 μl, 0.69 mmol) was added to a suspension of 4-(5-(4-(heptyloxy)phenyl)thiazol-2-yl)benzaldehyde (260 mg, 0.685 mmol) and methyl 2-((tert-butoxycarbonyl)amino)-2-(dimethoxyphosphoryl)acetate (185 mg, 0.62 mmol) in anhydrous THF (10 mL) under nitrogen, at −70° C. The reaction mixture was stirred at −70° C. for 1 h then at RT for 18 h. The reaction mixture was diluted with DCM (50 mL), washed with water (50 mL), passed through a phase separation cartridge and the organic phase concentrated in vacuo to afford a yellow solid. The solid was triturated with EA/EtOH (20 mL) and the collected solid washed with EtOH (10 mL) and Et2O to afford 284 mg (79%) of methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(5-(4-(heptyloxy)phenyl)thiazol-2-yl)phenyl)acrylate as a yellow solid. LCMS-ESI (m/z) calculated for C31H38N2O5S: 550.7. found 551.0 [M+H]+, tR=3.11 min. (Method 8).

Workup

  1. waitat RT for 18 h
  2. washwashed with water (50 mL)
  3. custompassed through a phase separation cartridge
  4. concentrationthe organic phase concentrated in vacuo
  5. customto afford a yellow solid
  6. customThe solid was triturated with EA/EtOH (20 mL)
  7. washthe collected solid washed with EtOH (10 mL) and Et2O

Sources & evidence

ORD record
ord-dbbe405acedb4c56a32290b09ff14e8d
Source dataset
uspto-grants-2015_11
Patent number
US09187522B2

Reaction notes

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