Triphenylphosphine → 7-{2-[3-(2-Ethoxycarbonyl-ethyl)-benzo[b]thiophen-6-yloxy]-ethyl}-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester

HRID 985491Notes

Reaction equation

HRID 985491 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][S:7][C:6]=2[CH:17]=1.[C:18]([O:22][C:23]([N:25]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([CH2:35][CH2:36]O)[N:33]=2)[CH2:28][CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[C:18]([O:22][C:23]([N:25]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([CH2:35][CH2:36][O:1][C:2]3[CH:3]=[CH:4][C:5]4[C:9]([CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][S:7][C:6]=4[CH:17]=3)[N:33]=2)[CH2:28][CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 11288155Ethyl 3-(6-hydroxybenzo[B]thiophen-3-YL)propanoateHCID 58230650tert-Butyl 7-(2-hydroxyethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

Product 1

HCID 695481007-{2-[3-(2-Ethoxycarbonyl-ethyl)-benzo[b]thiophen-6-yloxy]-ethyl}-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 3-(6-hydroxybenzo[b]thiophen-3-yl)propanoate (207 mg, 82.6 mmol), 7-(2-hydroxy-ethyl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (276 mg, 99.2 mmol) and triphenylphosphine (435 mg, 165 mmol) were dissolved in THF (15 ml) and stirred for 15 minutes under argon atmosphere at 0° C. Then, diisopropyl azodicarboxylate (0.325 ml, 165 mmol) was added to the mixture. After stirring overnight under argon, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was dried with sodium sulfate, filtered and evaporated under vacuum. The crude product was chromatographied over silica gel to yield 338 mg (80%) of 7-{2-[3-(2-Ethoxycarbonyl-ethyl)-benzo[b]thiophen-6-yloxy]-ethyl}-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester. NMR 1H Cl3CD δ: 7.59 (d, 1H, J=8.8 Hz), 7.33 (m, 2H), 7.00 (dd, 1H, J=2.3, 8.8 Hz), 6.93 (m, 2H), 4.42 (t, 2H, J=6.7 Hz), 4.14 (m, 2H), 3.76 (m, 2H), 3.22 (m, 2H), 3.12 (m, 2H), 2.73 (m, 4H), 1.92 (m, 2H) 1.51 (s, 9H), 1.26 (m, 3H).

Workup

  1. stirringAfter stirring overnight under argon
  2. customthe reaction mixture was partitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. filtrationfiltered
  5. customevaporated under vacuum

Sources & evidence

ORD record
ord-33822e3c4f8a49a9b6944b1b001a95d5
Source dataset
uspto-grants-2005_03
Patent number
US06872730B2

Reaction notes

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