Trifluoroacetic acid → HCID 66811393, compound

HRID 1099208Notes

Reaction equation

HRID 1099208 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[O:9][C:8]([C@H:10]3[C@@H:15]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH2:14][CH2:13][CH2:12][N:11]3C(OC(C)(C)C)=O)=[N:7][N:6]=2)[CH2:2]1.[C:29](Cl)(=[O:34])[CH2:30][CH2:31][CH2:32][CH3:33].C(N(CC)CC)C.C(O)(C(F)(F)F)=O>ClCCl>[C:29]([N:1]1[CH2:4][CH:3]([C:5]2[O:9][C:8]([C@H:10]3[C@@H:15]([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH2:14][CH2:13][CH2:12][NH:11]3)=[N:7][N:6]=2)[CH2:2]1)(=[O:34])[CH2:30][CH2:31][CH2:32][CH3:33]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 61186Valeryl chlorideHCID 66811232HCID 66811232, compound

Product 1

HCID 66811393HCID 66811393, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl cis-2-(5-azetidin-3-yl-1,3,4-oxadiazol-2-yl)-3-phenylpiperidine-1-carboxylate (3C.3, 20.0 mg, 0.05 mmol) in dichloromethane (1 ml) was added valeryl chloride (0.007 ml, 0.06 mmol) and triethylamine (0.007 ml, 0.05 mmol). The reaction was allowed to stir for 0.5 h. TFA (0.3 ml) was added to the reaction and allowed to stir for an additional 1 h. The reaction was concentrated and purified via reverse phase preparative HPLC. Product containing fractions were treated with aqueous sodium bicarbonate. The product was extracted with EtOAc, washed with brine, dried over sodium sulfate, filtered, and concentrated to yield cis-2-[5-(1-pentanoylazetidin-3-yl)-1,3,4-oxadiazol-2-yl]-3-phenylpiperidine (52%). 1H NMR (400 MHz, CD3OD) δ 7.22-7.08 (m, 5H), 4.59 (d, J=5.2 Hz, 1H), 4.47 (dt, J=4.4 Hz, 1H), 4.23 (q, J=9.3 Hz, 1H), 4.11 (dd, J=9.0, 5.8 Hz, 0.5H), 4.05 (dd, J=8.4, 5.6 Hz, 0.5H), 3.95 (m, 1H), 3.84 (m, 1H), 3.33 (m, 2H), 2.89 (m, 1H), 2.34 (m, 1H), 2.10 (m, 2H), 1.92 (m, 2H), 1.74 (m, 1H), 1.54 (quint, J=7.5 Hz, 2H), 1.35 (m, 2H), 0.93 (dt, J=7.4, 2.9 Hz, 3H).

Workup

  1. stirringto stir for an additional 1 h
  2. concentrationThe reaction was concentrated
  3. custompurified via reverse phase preparative HPLC
  4. additionProduct containing fractions
  5. additionwere treated with aqueous sodium bicarbonate
  6. extractionThe product was extracted with EtOAc
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-47fc7b7c339242708b44a0e50cb59f19
Source dataset
uspto-grants-2012_03
Patent number
US08143405B2

Reaction notes

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