4-Nitrobenzoic Acid → HCID 118207285, compound

HRID 1507200Notes

Reaction equation

HRID 1507200 reaction equation
CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:32]([C:35]1[CH:43]=[CH:42][C:38]([C:39]([OH:41])=[O:40])=[CH:37][CH:36]=1)([O-:34])=[O:33].[CH2:44]([O:51][C:52]1[CH:57]=[CH:56][C:55]([CH:58]2[CH2:63][CH2:62][N:61]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:60][CH:59]2O)=[CH:54][CH:53]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>O1CCCC1.O>[CH2:44]([O:51][C:52]1[CH:57]=[CH:56][C:55]([C@H:58]2[CH2:63][CH2:62][N:61]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:60][C@H:59]2[O:40][C:39](=[O:41])[C:38]2[CH:37]=[CH:36][C:35]([N+:32]([O-:34])=[O:33])=[CH:43][CH:42]=2)=[CH:54][CH:53]=1)[C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

7

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 53401373HCID 53401373, compound

Product 1

HCID 118207285HCID 118207285, compoundYield 53.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of diethylazodicarboxylate (12.9 mL, 81 mmol of 40% toluene solution), triphenyl phosphine (22 mL, 83 mmol), 4-nitrobenzoic acid (6.97 g, 42 mmol) and 200 mL tetrahydrofuran was stirred for 10 min under an Ar atmosphere. Then was added a solution of tert-butyl 4-(4-(benzyloxy)phenyl)-3-hydroxypiperidine-1-carboxylate (Example 56, step D, 8 g, 20.9 mmol) in tetrahydrofuran (100 mL) and the resulting mixture was stirred at rt overnight. It was then diluted with water and extracted twice with 50 mL ethyl acetate. The combined organic fractions were dried over Na2SO4, filtered, and evaporated to dryness. The residue was purified via silica gel chromatography (750 μm column, eluting with 0-50% ethyl acetate/hexane) to yield 6 gms (±)-rel-(3S,4R)-tert-butyl 4-(4-(benzyloxy)phenyl)-3-(4-nitrobenzoyloxyl)piperidine-1-carboxylate. LCMS (Method F) RT 2.68 min (87% AP), m/z 476.8 (MH+−t-butyl).

Workup

  1. stirringthe resulting mixture was stirred at rt overnight
  2. extractionextracted twice with 50 mL ethyl acetate
  3. dry with materialThe combined organic fractions were dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified via silica gel chromatography (750 μm column, eluting with 0-50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-237c137395e44667ad41efa485e91228
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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