Sodium borohydride → 3-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-carboxamido)-3-(hydroxymethyl)pyridin-2-yl)benzoic acid

HRID 2188968Notes

Reaction equation

HRID 2188968 reaction equation
[BH4-].[Na+].[F:3][C:4]1([F:38])[O:8][C:7]2[CH:9]=[CH:10][C:11]([C:13]3([C:16]([NH:18][C:19]4[N:24]=[C:23]([C:25]5[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=5)[C:28]([OH:30])=[O:29])[C:22]([C:34](OC)=[O:35])=[CH:21][CH:20]=4)=[O:17])[CH2:15][CH2:14]3)=[CH:12][C:6]=2[O:5]1>C1COCC1>[F:38][C:4]1([F:3])[O:8][C:7]2[CH:9]=[CH:10][C:11]([C:13]3([C:16]([NH:18][C:19]4[N:24]=[C:23]([C:25]5[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=5)[C:28]([OH:30])=[O:29])[C:22]([CH2:34][OH:35])=[CH:21][CH:20]=4)=[O:17])[CH2:14][CH2:15]3)=[CH:12][C:6]=2[O:5]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydride2×HCID 591659443-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-(methoxycarbonyl)pyridin-2-yl)benzoic acid

Product 1

HCID 591661043-(6-(1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-carboxamido)-3-(hydroxymethyl)pyridin-2-yl)benzoic acidYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

NaBH4 (53 mg, 1.4 mmol) was added to a solution of 3-(6-(1-(2,2-difluorobenzo-[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-(methoxycarbonyl)pyridin-2-yl)benzoic acid (140 mg, 0.28 mmol) in THF (3 mL). The reaction was stirred at 50° C. for 5 hours. Additional NaBH4 (53 mg, 1.4 mmol) was added and the reaction was stirred at 50° C. overnight. The reaction was quenched by the addition of water and the reaction mixture was partitioned between CH2Cl2 and 1N HCl. The organic layer was dried (MgSO4) and concentrated. CH2Cl2 was added to the residue and a precipitate formed which was filtered to obtain the product as a white solid (52 mg, 40%). ESI-MS m/z calc. 468.1. found 469.5 (M+1)+. Retention time 1.64 minutes. 1H NMR (400 MHz, DMSO-d6) δ 9.10 (s, 1H), 8.06 (d, J=1.5 Hz, 1H), 8.01-7.93 (m, 3H), 7.76 (d, J=7.5 Hz, 1H), 7.57-7.54 (m, 2H), 7.40-7.34 (m, 2H), 5.33 (s, 1H), 4.38 (s, 2H), 1.53-1.51 (m, 2H), 1.19-1.16 (m, 2H).

Workup

  1. stirringthe reaction was stirred at 50° C. overnight
  2. customThe reaction was quenched by the addition of water
  3. customthe reaction mixture was partitioned between CH2Cl2 and 1N HCl
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated
  6. additionCH2Cl2 was added to the residue
  7. customa precipitate formed which
  8. filtrationwas filtered

Sources & evidence

ORD record
ord-a590a227fdc040fdbbf1fbbaa022fad0
Source dataset
uspto-grants-2012_12
Patent number
US08324207B2

Reaction notes

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