3-Methyl-5-(3-tetradecyl-ureido)-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester → Tetradecyl isocyanate

HRID 1829612Notes

Reaction equation

HRID 1829612 reaction equation
C(OC(C1C(C)=C(C(OCC2C=CC=CC=2)=O)SC=1N[C:14]([NH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[O:15])=O)(C)(C)C.CC(OC(C1SC(NC(NCCCCCCCC)=O)=C(C(OC(C)(C)C)=O)C=1C)=O)CCCCCC>CCOC(C)=O>[CH2:17]([N:16]=[C:14]=[O:15])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]

Participants

4

Reactant 2

HCID 210307463-Methyl-5-(3-tetradecyl-ureido)-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl esterHCID 696422973-Methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester

Product 1

HCID 3485710Tetradecyl isocyanate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(5.1) To a stirring solution of 5-amino-3-methyl-thiophene-2,4-dicarboxylic acid 2-octyl ester 4-tert-butyl ester (348 mg, 0.94 mmol) and DBU (0.35 mL, 360 mg, 2.4 mmol) in CH2Cl2 (10 mL) was added octyl isocyanate (0.166 mL, 146 mg, 0.94 mmol). The reaction was stirred RT for 16 h, and then solvent was removed under reduced pressure. The product was purified by column chromatography (5:1; hexanes:EtOAc) to give 431 mg of a solid (87%): Mp 92.0-94.0° C.; 1H NMR (CDCl3) δ 12.30 (s, 1H), 8.64 (s, 1H), 5.30 (t, 1H, J=6.0 Hz), 4.25 (t, 2H, J=6.4 Hz), 3.29 (q, 2H, J=6.0 Hz), 2.74 (s, 3H), 1.90-1.50 (m, 4H), 1.61 (s, 9H), 1.28 (bs, 20H), 0.88 (m, 6H). MS (EI): 525.1 (m+). 3-Methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.2) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with octyl isocyanate (3.83 mL, 3.37 g, 21.7 mmol) afforded 3.42 g of a solid (38%) after column chromatography (9:1; hexanes:EtOAc): Mp 119.0-120.0° C.; 1H NMR (CDCl3) δ 11.03 (s, 1H), 7.50-7.20 (m, 5H), 5.27 (s, 2H), 5.03 (vt, 1H), 3.29 (q, 2H, J=6.6 Hz), 2.71 (s, 3H), 1.63-1.40 (m, 2H), 1.57 (s, 9H), 1.26 (bs, 10H), 0.87 (t, 3H, J=6.6 Hz). MS (EI): 502.8 (m+). 3-Methyl-5-(3-tetradecyl-ureido)-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.3) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with tetradecyl isocyanate (0.33 mL, 287 mg, 1.2 mmol) afforded 253 mg of a solid (36%) after column chromatography (9:1; hexanes:EtOAc): Mp 104.5-106.0° C.; 1H NMR (CDCl3) δ 11.04 (s, 1H), 7.50-7.20 (m, 5H), 5.27 (s, 2H), 5.14 (t, 1H, J=6.2 Hz), 3.29 (q, 2H, J=6.2 Hz), 2.71 (s, 3H), 1.65-1.40 (m, 2H), 1.57 (s, 9H), 1.25 (bs, 22H), 0.88 (t, 3H, J=6.0 Hz). MS (EI): 587.1 (m+). 5-(3-Hexadecyl-ureido)-3-methyl-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.4) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with hexadecyl isocyanate (0.37 mL, 321 mg, 1.2 mmol) afforded 218 mg of a solid (30%) after column chromatography (9:1; hexanes:EtOAc): Mp 104.0-105.0° C.; 1H NMR (CDCl3) δ 11.04 (s, 1H), 7.50-7.20 (m, 5H), 5.27 (s, 2H), 5.14 (t, 1H, J=6.2 Hz), 3.29 (q, 2H, J=6.2 Hz), 2.71 (s, 3H), 1.65-1.40 (m, 2H), 1.57 (s, 9H), 1.25 (bs, 26H), 0.88 (t, 3H, J=6.0 Hz). MS (EI): 615.1 (m+). 5-(3-Dodecyl-ureido)-3-methyl-thiophene-2,4-dicarboxylic acid 2-benzyl ester 4-tert-butyl ester. (5.5) The same method as for the preparation of 3-methyl-5-(3-octyl-ureido)-thiophene-2,4-dicarboxylic acid 4-tert-butyl ester 2-octyl ester was employed. Thus, acylation with decyl isocyanate (0.29 mL, 254 mg, 1.2 mmol) afforded 265 mg of a solid (40%) after column chromatography (9:1; hexanes:EtOAc): Mp 106.8-108.0° C.). 1H NMR (CDCl3) δ 11.04 (s, 1H), 7.45-7.26 (m, 5H), 5.27 (s, 2H), 5.24 (t, 1H, J=5.6 Hz), 3.28 (q, 2H, J=6.6 Hz), 2.72 (s, 3H), 1.60-1.40 (m, 2H), 1.57 (s, 9H), 1.25 (bs, 18H), 0.88 (t, 3H, J=6.4 Hz). MS (EI): 559.0 (m+).

Sources & evidence

ORD record
ord-2780b6769bde4fe6bf8bea9d8f682dfc
Source dataset
uspto-grants-2006_06
Patent number
US07064122B2

Reaction notes

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