Triethylamine → HCID 11202011, compound

HRID 1173006

Reaction equation

HRID 1173006 reaction equation
[CH:1]([C:4]1[N:5]=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[S:7][C:8]=1[CH2:9]O)([CH3:3])[CH3:2].CCN(CC)CC.CS(Cl)(=O)=O.[NH2:33][C:34]1[CH:39]=[CH:38][C:37]([C@@H:40]2[CH2:42][C@H:41]2[C:43]([OH:45])=[O:44])=[CH:36][CH:35]=1>ClCCl.O>[CH:1]([C:4]1[N:5]=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[S:7][C:8]=1[CH2:9][NH:33][C:34]1[CH:35]=[CH:36][C:37]([C@@H:40]2[CH2:42][C@H:41]2[C:43]([OH:45])=[O:44])=[CH:38][CH:39]=1)([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 587657624-Isopropyl-2-[4-(trifluoromethyl)phenyl]thiazole-5-methanolHCID 68668314(1R,2R)-2-(4-aminophenyl)cyclopropane-1-carboxylic acid

Product 1

HCID 11202011HCID 11202011, compoundYield 19.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of {(4-isopropyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methanol (0.10 g, 0.331 mmol) in dichloromethane (3 mL) was added Et3N (0.04 g, 0.39 mmol) and the mixture cooled to 0° C. The mixture stirred for 15 min after which methanesulfonyl chloride (0.04 g, 0.36 mmol) was added followed 30 min later by the addition of racemic-(trans)-2-(4-aminophenyl)cyclopropanecarboxylic acid (I-1) (0.09 g, 0.49 mmol). The solution stirred for 24 h after which it was poured into H2O, the organics extracted with dichloromethane, dried over MgSO4, and the solvents reduced in vacuo. The crude material was purified on silica gel eluting with an increasing gradient from hexanes to 30% ethyl acetate/hexanes to give the title compound as a yellow powder (0.03 g, 16%). 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J=8.3 Hz, 2H), 7.65 (d, J=8.2 Hz, 2H), 6.98 (d, J=8.4 Hz, 2H), 6.62 (d, J=8.6 Hz, 2H), 4.47 (s, 2H), 3.50-3.47 (m, 1H), 3.18-3.15 (m, 1H), 2.53-2.51 (m, 1H), 1.80-1.77 (m, 1H), 1.61-1.58 (m, 1H), 1.37-1.26 (m, 7H).

Workup

  1. additionwas added
  2. extractionthe organics extracted with dichloromethane
  3. dry with materialdried over MgSO4
  4. customThe crude material was purified on silica gel eluting with an increasing gradient from hexanes to 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-ee78b6a53a9e4997a25bbcdb804911dd
Source dataset
uspto-grants-2010_11
Patent number
US07834013B2

Linked notes

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