Hydroxylamine → 1-{[(4S)-2-(hydroxyamino)-4-phenylpentyl]sulfonyl}4-[4-(trimethylsilylethynyl)phenyl]piperazine

HRID 859926Notes

Reaction equation

[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[C:18][Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Cl[Si](C)(C)C.[C:38]1([C@@H:44]([CH3:48])[CH2:45][CH:46]=O)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[NH2:49][OH:50]>C1COCC1>[OH:50][NH:49][CH:46]([CH2:45][C@@H:44]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH3:48])[CH2:1][S:2]([N:5]1[CH2:6][CH2:7][N:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[C:18][Si:19]([CH3:21])([CH3:20])[CH3:22])=[CH:13][CH:12]=2)[CH2:9][CH2:10]1)(=[O:4])=[O:3]

Participants

Conditions

Temperature: -40 °C

Procedure

To a stirred suspension of 1-(methylsulfonyl)-4-[4-(trimethylsilylethynyl)phenyl]piperazine (673 mg, 2 mmol) in THF (13 mL) at −40° C., was added dropwise a solution of LiHMDS in THF (4.5 mL, 11.0M solution, 4.5 mmol). The resulting suspension was stirred at −40° C. for 10 minutes before being treated with chlorotrimethylsilane (254 μL, 2 mmol). The solution was then maintained at −40° C. for 10 minutes before being treated with a solution of (3S)-3-phenylbutanal (385 mg, 2.6 mmol, CAS number 53531-194) in THF (8 mL). The solution was allowed to warm to −15° C. over 1 hour before being quenched with a solution of hydroxylamine (1.23 mL, 50% aqueous solution in water, 20 mmol). The reaction was stirred for 3 hours at RT. The reaction was partitioned between ethyl acetate (30 mL) and water (30 mL). The combined organic extracts were then dried, (sat. brine and MgSO4), filtered and concentrated in vacuo. The residue was then purified by flash chromatography (silica, 30–40% ethyl acetate in iHexane) to give 1-{[(4S)-2-(hydroxyamino)-4-phenylpentyl]sulfonyl}-4-[4-(trimethylsilylethynyl)phenyl]piperazine (720 mg, 1.44 mmol, 68% @ 94 wt %).

Workup

temperatureThe solution was then maintained at −40° C. for 10 minutes
temperatureto warm to −15° C. over 1 hour
stirringThe reaction was stirred for 3 hours at RT
customThe reaction was partitioned between ethyl acetate (30 mL) and water (30 mL)
dry with materialThe combined organic extracts were then dried, (sat. brine and MgSO4),
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was then purified by flash chromatography (silica, 30–40% ethyl acetate in iHexane)

Sources & evidence

ORD record: ord-158455fd4d8945a1a062f09828b48e03
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07153857B2

Reaction notes

Loading…