Isopropanol → Isopropyl-N,N,N',N'-tetraisopropylphosphorodiamidite

HRID 2168586Notes

Reaction equation

[CH:1]([N:4]([P:8]([N:10]([CH:14]([CH3:16])[CH3:15])[CH:11]([CH3:13])[CH3:12])Cl)[CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:24][CH:25]([OH:27])[CH3:26]>C(OCC)C>[CH:25]([O:27][P:8]([N:10]([CH:14]([CH3:16])[CH3:15])[CH:11]([CH3:13])[CH3:12])[N:4]([CH:5]([CH3:7])[CH3:6])[CH:1]([CH3:3])[CH3:2])([CH3:26])[CH3:24]

Participants

Conditions

Temperature: 0 °C

Procedure

Bis(diisopropylamino)chlorophosphine (19, 250.1 g, 937 mmol) was dissolved in anhydrous ethyl ether (3.6 L) and triethylamine (190 g, 1.87 mol) was introduced. The turbid mixture was cooled at 0° C. and a solution of 2-propanol (225 g, 287 mL) in ether (200 mL) was added via a funnel. The resulting cloudy mixture was stirred at room temperature for 5.5 hours. The reaction was complete by checking with 31P NMR (δ=116.10 ppm, S). White solid (triethylamine HCl salt) was removed by filtration. The filtrate was concentrated to furnish a pale brown liquid (272 g, quantitative) and used for next step without further purification. Note that the P(III)-reagent can be purified by vacuum distillation (bp 84-86° C., 5 mm Hg) if desired to furnish a colorless clear oil. 1H NMR (CDCl3): δ 3.91 (m, 1H), 3.51 (m, 4H), 1.19 (d, 6H, J=6 Hz), 1.16 (24H, m). 31P NMR (CDCl3): δ 116.1.

Workup

customWhite solid (triethylamine HCl salt) was removed by filtration
concentrationThe filtrate was concentrated
customto furnish a pale brown liquid (272 g, quantitative)
customused for next step without further purification
distillationcan be purified by vacuum distillation (bp 84-86° C., 5 mm Hg)
customto furnish a colorless clear oil

Sources & evidence

ORD record: ord-66f28ccdc0334eb5bfe58de4bd3dff4e
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09045520B2

Reaction notes

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