Lithium borohydride → 1-(3-Hydroxy-propyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 2055800Notes

Reaction equation

HRID 2055800 reaction equation
[Li+].[BH4-].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]2[N:16]([CH2:29][CH2:30][C:31](OC)=[O:32])[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[C:12]=2[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>C1COCC1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]2[N:16]([CH2:29][CH2:30][CH2:31][OH:32])[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:26])[F:27])=[CH:21][CH:20]=3)[C:12]=2[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 4148881Lithium borohydride2×HCID 684627001-(2-Methoxycarbonyl-ethyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 684611921-(3-Hydroxy-propyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of LiBH4 (26 mg, 1.2 mmol) in THF (0.5 mL) was added to a 0° C. solution of 1-(2-methoxycarbonyl-ethyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (317 mg, 0.70 mmol) in THF (4.0 mL). The mixture was stirred for 5 min then additional LiBH4 (15 mg) was added and stirring continued for 17 h. The mixture was partitioned between EtOAc (80 mL) and saturated aqueous NaHCO3 (20 mL). The aqueous layer was extracted with EtOAc (2×20 mL). The combined extracts were dried over Na2SO4 and concentrated. Column chromatography (silica, 0-8% MeOH/CH2Cl2) afforded 268 mg (95%) of the title compound. HPLC (reverse phase conditions), tR=6.82 min. MS (electrospray): m/z calculated for C21H26F3N3O3 [M++Na] 448.18, found 448.10. 1H NMR (CDCl3, 400 MHz): 7.73 (br d, J=8.2 Hz, 2H), 7.65 (br s, 2H), 4.64 (br s, 2H), 4.21 (t, J=6.4 Hz, 2H), 3.76 (br s, 2H), 3.66 (t, J=5.7 Hz, 2H), 2.73 (br t, J=5.4 Hz, 2H), 2.04 (q, J=6.1, 2H), 1.48 (s, 9H).

Workup

  1. stirringstirring
  2. waitcontinued for 17 h
  3. customThe mixture was partitioned between EtOAc (80 mL) and saturated aqueous NaHCO3 (20 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (2×20 mL)
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ee444e3a0e7d4b19aecb9d4cada1c663
Source dataset
uspto-grants-2008_02
Patent number
US07332494B2

Reaction notes

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