methyl sulfide THF → (3R)-8-Cyclopropyl-6-hydroxymethyl-7-(Naphtalen-1-ylmethyl)-5-oxo-2,3-dihydro-5h-thiazolo[3,2-a]pyridine-3-carboxylic Acid Methyl Ester

HRID 606641Notes

Reaction equation

HRID 606641 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[N:9]2[C:10](=[O:30])[C:11]([CH:28]=[O:29])=[C:12]([CH2:17][C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH:21]=[CH:20][CH:19]=3)[C:13]([CH:14]3[CH2:16][CH2:15]3)=[C:8]2[S:7][CH2:6]1)=[O:4].CSC.C1COCC1>O1CCCC1>[CH3:1][O:2][C:3]([C@H:5]1[N:9]2[C:10](=[O:30])[C:11]([CH2:28][OH:29])=[C:12]([CH2:17][C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH:21]=[CH:20][CH:19]=3)[C:13]([CH:14]3[CH2:16][CH2:15]3)=[C:8]2[S:7][CH2:6]1)=[O:4]

Participants

4

Reactant 2

HCID 56833473methyl sulfide THFHCID 866117918-Cyclopropyl-6formyl-7-naphthalen-1-ylmethyl-5-oxo-2,3-dihydro-5h-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester

Product 1

HCID 67048351(3R)-8-Cyclopropyl-6-hydroxymethyl-7-(Naphtalen-1-ylmethyl)-5-oxo-2,3-dihydro-5h-thiazolo[3,2-a]pyridine-3-carboxylic Acid Methyl EsterYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The formylated 2-pyridone 2 (100 mg, 0.239 mmol) was dissolved in tetrahydrofuran (3.30 mL) at 0° C. Then 2M BH3 DMS THF (0.131 mL, 0.262 mmol) was added dropwise during 15 min. The mixture was then stirred in room temperature during 1 h, quenched with methanol and concentrated twice from methanol. The residue was purified through flash column chromatography (CH2Cl2:MeOH, 9:1). Co-concentration from CH2Cl2 (×2) resulted in 4 as white foam (80.6 mg, yield: 80%). 1H-NMR (400 Mhz, CDCl3) δ 8.16 (d, J=8.23 Hz, 1H, ArH), 7.87 (d, J=7.96 Hz, 1H, ArH), 7.71 (d, J=8.14 Hz 1H, ArH), 7.64-7.48 (m, 2H, ArH) 7.30 (m, 1H, ArH) 6.83 (d, J=6.95 Hz, 1H, ArH), 5.68 (d, J=7.04 Hz, 1H, CHCO2Me), 4.72 (d, J=16.28 Hz, 1H, Nph-CH2), 4.61 (d, J=16.28 Hz, 1H, Nph-CH2) 4.58-4.36 (m, 2H, CH2OH) 3.84 (s, 3H, CH3) 3.76-3.62 (m, 2H, SCH2, OH) 3.60-3.50 (m, 1H, SCH2) 1.46-1.34 (m, 1H, CH-cyclopropyl) 0.65 (ss, 2H, CH2-cyklopropyl) 0.51 (ss, 2H, CH2-cyklopropyl) 13C-NMR (100 Mhz, CDCl3) δ 168.61, 161.87, 152.08, 146.62, 134.11, 133.76, 131.77, 128.94, 127.17, 126.37, 125.92, 125.66, 125.63, 124.26, 122.98, 114.93, 63.27, 58.78, 53.40, 31.77, 31.58, 11.81, 7.53, 7.20.

Workup

  1. customquenched with methanol
  2. concentrationconcentrated twice from methanol
  3. customThe residue was purified through flash column chromatography (CH2Cl2:MeOH, 9:1)
  4. concentrationCo-concentration from CH2Cl2 (×2)

Sources & evidence

ORD record
ord-98e1ae38f1ae4e35a016a35b2b1df60b
Source dataset
uspto-grants-2011_03
Patent number
US07915417B2

Reaction notes

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