Lithium hydroxide, monohydrate → tert-butyl 6-chloro-3-(hydroxymethyl)-8-(phenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate

HRID 2179416Notes

Reaction equation

HRID 2179416 reaction equation
C([O:4][CH2:5][CH:6]1[N:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][C:9]2[C:19]3[CH:25]=[C:24]([S:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)(=[O:28])=[O:27])[CH:23]=[C:22]([Cl:35])[C:20]=3[O:21][C:8]=2[CH2:7]1)(=O)C.O.[OH-].[Li+]>CO.O>[Cl:35][C:22]1[C:20]2[O:21][C:8]3[CH2:7][CH:6]([CH2:5][OH:4])[N:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][C:9]=3[C:19]=2[CH:25]=[C:24]([S:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH:23]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68109871tert-butyl 3-(acetoxymethyl)-6-chloro-8-(phenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate

Product 1

HCID 68109614tert-butyl 6-chloro-3-(hydroxymethyl)-8-(phenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylateYield 80.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To the crude product of step K (110 mg, 0.22 mmol) in methanol (5 mL) and water (5 mL) at 0° C. was added lithium hydroxide monohydrate (92 mg, 2.2 mmol). The solution was stirred at ambient temperature for 2 h then concentrated in vacuo. Water (10 mL) was added and the mixture extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to give the crude product. Purification by flash column chromatography (SiO2, 9:1 to 7:3, hexanes/ethyl acetate) afforded tert-butyl 6-chloro-3-(hydroxymethyl)-8-(phenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (85 mg, 80%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) δ 7.98-7.95 (m, 3H), 7.84 (d, J=1.5 Hz, 1H), 7.56-7.51 (m, 3H), 4.93 (br s, 2H), 4.13-4.10 (m, 1H), 3.64-3.61 (m, 2H), 3.17-3.08 (m, 1H), 2.88 (d, J=17.4 Hz, 1H), 1.85 (br s, 1H), 1.53 (s, 9H).

Workup

  1. concentrationthen concentrated in vacuo
  2. additionWater (10 mL) was added
  3. extractionthe mixture extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give the crude product
  8. customPurification by flash column chromatography (SiO2, 9:1 to 7:3, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-6bb7cd4805244398a532135aba9f5234
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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