Tetrahydrofuran → HCID 16042872, compound

HRID 545190Notes

Reaction equation

HRID 545190 reaction equation
C[O:2][C:3](=[O:43])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[CH:11]=[C:12]3[C:39](=[CH:40][CH:41]=2)[O:38][C:15]2([CH2:20][CH2:19][N:18]([C:21]([C:23]4[CH:32]=[C:31]5[C:26]([CH:27]=[CH:28][N:29]=[C:30]5[CH:33]5[CH2:35][CH2:34]5)=[C:25]([O:36][CH3:37])[CH:24]=4)=[O:22])[CH2:17][CH2:16]2)[CH2:14][C:13]3=[O:42])[CH:5]=1.C1COCC1.[OH-].[Na+]>CO.C(Cl)(Cl)Cl.Cl>[CH:33]1([C:30]2[C:31]3[C:26](=[C:25]([O:36][CH3:37])[CH:24]=[C:23]([C:21]([N:18]4[CH2:19][CH2:20][C:15]5([CH2:14][C:13](=[O:42])[C:12]6[C:39](=[CH:40][CH:41]=[C:10]([C:6]7[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=7)[C:3]([OH:43])=[O:2])[CH:11]=6)[O:38]5)[CH2:16][CH2:17]4)=[O:22])[CH:32]=3)[CH:27]=[CH:28][N:29]=2)[CH2:35][CH2:34]1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 67170901HCID 67170901, compound

Product 1

HCID 16042872HCID 16042872, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent2×HCID 6212ChloroformSolvent

Procedure

3-{1′-[(1-Cyclopropyl-5-methoxy-isoquinolin-7-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}benzoic acid methyl ester (2.00 g, 3.47 mmol) was dissolved in MeOH (20 mL), THF (10 mL) and 1N NaOH aq. (6 mL) was added thereto. After stirred at room temperature for 3 days, the reaction mixture was diluted with CHCl3, MeOH and 1N HCl aq. (6 mL). The aqueous layer was extracted with CHCl3 and the combined organic layer was dried over MgSO4. The desiccant was removed through filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/EtOAc=5/5 to 0/10, then CHCl3/MeOH=10/0 to 88/12) to obtain the intended compound as a colorless solid. 1H-NMR (400 MHz, DMSO-d6) δ: 8.36 (1.0H, d, J=5.9 Hz), 8.13 (1.0H, s), 8.07 (1.0H, s), 7.99-7.94 (2.0H, m), 7.93-7.85 (2.0H, m), 7.74 (1.0H, d, J=5.9 Hz), 7.60-7.53 (1.0H, m), 7.23 (1.0H, d, J=9.0 Hz), 7.19 (1.0H, s), 4.43-4.25 (1.0H, br m), 4.01 (3.0H, s), 3.67-3.13 (3.0H, m), 2.98-2.87 (1.0H, m), 2.95 (2.0H, s), 2.18-2.05 (1.0H, br m), 2.00-1.78 (3.0H, m), 1.16-1.01 (4.0H, m). MS [M+H]+=563.

Workup

  1. extractionThe aqueous layer was extracted with CHCl3
  2. dry with materialthe combined organic layer was dried over MgSO4
  3. customThe desiccant was removed through filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/EtOAc=5/5 to 0/10

Sources & evidence

ORD record
ord-3c760b5edb5f4bbd81c50c66267b79c2
Source dataset
uspto-grants-2011_05
Patent number
US07935712B2

Reaction notes

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