Hydroxylamine → HCID 59776373, compound

HRID 1008776Notes

Reaction equation

HRID 1008776 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C(OP(Cl)(OCC)=O)C.[CH3:37][C:38]([CH3:50])([CH2:41][C:42]#[C:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[CH:39]=O.[NH2:51][OH:52]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH2:17][CH:39]([NH:51][OH:52])[C:38]([CH3:37])([CH3:50])[CH2:41][C:42]#[C:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)(=[O:15])=[O:16])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 787HydroxylamineHCID 13139Diethyl chlorophosphateHCID 6690391-(4-Fluorophenyl)-4-(methylsulfonyl)piperazine2×HCID 2733832Lithium HexamethyldisilazideHCID 105594702,2-Dimethyl-5-phenylpent-4-ynal

Product 1

HCID 59776373HCID 59776373, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-(4-fluorophenyl)-4-(methylsulfonyl)piperazine (Intermediate B1; 600 mg; 2.32 mmol) in THF (10 mL) was added Lithiumbis(trimethylsilyl)amide (4.65 mL of a 1.00 M solution in THF; 4.65 mmol) at −78° C. under N2. After 30 min, diethylchlorophosphate (0.38 mL; 2.56 mmol) was added and the mixture was stirred at −78° C. for one hour. A solution of 2,2-dimethyl-5-phenylpent-4-ynal (prepared as described by Cossy et al., 1997, Journal of Organic Chemistry, 62(23), 7900-7901, 432 mg; 2.32 mmol) in THF (5 mL) was cannulated and the reaction mixture was allowed to warm to rt and stirred for 12 h. Hydroxylamine (4.1 mL; 70 mmol was then added and the mixture was heated at 60° C. for 3 h. It was finally concentrated under reduced pressure, redissolved in is EtOAc, washed with a saturated solution of NH4Cl and with brine, dry over magnesium sulfate, filtrated and concentrated. Purification of the crude by flash chromatography on silica (EtOAc:c-Hex; gradient from 20:80 to 50:50) gave the title compounds as a yellow oil (710 mg, 66% yield). HPLC, Rt: 4.15 min (purity: 95.9%). LC/MS, M+(ESI): 460.2. 1H NMR (DMSO-d6) δ: 7.37 (m, 2H), 7.23 (m, 3H), 6.96 (m, 2H), 6.86 (m, 2H), 3.60 (dd, J=14.2, 10.1 Hz, 1H), 3.61 (m, 4H), 3.34 (dd, J=10.1, 1.8 Hz, 1H), 3.12 (m, 5H), 2.37 (AB, J=15.9, Δ=49.3 Hz, 2H), 1.12 (s, 3H), 1.14 (s, 3H).

Workup

  1. customat −78° C.
  2. temperatureto warm to rt
  3. stirringstirred for 12 h
  4. addition70 mmol was then added
  5. temperaturethe mixture was heated at 60° C. for 3 h
  6. concentrationIt was finally concentrated under reduced pressure
  7. dissolutionredissolved in is EtOAc
  8. washwashed with a saturated solution of NH4Cl and with brine
  9. dry with materialdry over magnesium sulfate
  10. filtrationfiltrated
  11. concentrationconcentrated
  12. customPurification of the crude by flash chromatography on silica (EtOAc:c-Hex; gradient from 20:80 to 50:50)

Sources & evidence

ORD record
ord-bffa235ea5934f39b137446e132b0e54
Source dataset
uspto-grants-2011_07
Patent number
US07973039B2

Reaction notes

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