1,2-Dichloroethane → HCID 86661485, compound

HRID 1951955Notes

Reaction equation

HRID 1951955 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:16]([OH:18])=[O:17])[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O/[N:20]=[C:21](/[C:23]1[CH:40]=[CH:39][C:26]([CH2:27][N:28]2[CH2:31][CH:30]([C:32]([O:34][C:35]([CH3:38])(C)C)=[O:33])[CH2:29]2)=[CH:25][CH:24]=1)\[NH2:22].N1C=CC=[CH:43][C:42]=1C1C(C(F)(F)F)=C(C2ON=C(C3C=CC(CN4CC(C(O)=O)C4)=CC=3)N=2)ON=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl>CN(C)C=O>[C:1]1([C:7]2[CH:8]=[C:9]([C:16]([O:18][N:20]=[C:21]([C:23]3[CH:24]=[CH:25][C:26]([CH2:27][N:28]4[CH2:29][CH:30]([C:32]([O:34][CH2:35][CH2:38][CH2:42][CH3:43])=[O:33])[CH2:31]4)=[CH:39][CH:40]=3)[NH2:22])=[O:17])[S:10][C:11]=2[C:12]([F:14])([F:15])[F:13])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27833724-Phenyl-5-(trifluoromethyl)thiophene-2-carboxylic acidHCID 468359141-(4-(5-(3-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acidHCID 58504340HCID 58504340, compound

Product 1

HCID 86661485HCID 86661485, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-phenyl-5-(trifluoromethyl)thiophene-2-carboxylic acid (408 mg, 1.50 mmol), (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate, Int. 1 (458 mg, 1.50 mmol), HOBT (345 mg, 2.250 mmol), Hunig's Base (1.05 mL, 6.00 mmol), and EDC (431 mg, 2.25 mmol) in N,N-dimethylformamide (7.5 mL) was stirred at room temperature for 18 h. The reaction mixture was partitioned between ethyl acetate (120 mL) and a saturated aqueous solution of sodium bicarbonate (60 mL). The organic layer was washed with water (2×120 mL), washed with brine (120 mL), and dried over anhydrous magnesium sulfate. Concentration under reduced pressure afforded ten-butyl 1-(4-(N′-(4-phenyl-5-(trifluoromethyl)thiophene-2-carbonyloxy)carbamimidoyl)benzyl)azetidine-3-carboxylate (744 mg, 1.33 mmol, 89% yield) as a light peach colored solid that was used in the next step without further purification. HPLC: ret. time=3.26 minutes (YMC Combi S-5 4.6×50 mm ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS: (M+H)=560.25.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (120 mL)
  2. washThe organic layer was washed with water (2×120 mL)
  3. washwashed with brine (120 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-5de219a56f594c529d40a09db376037d
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

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