Methyl chloroformate → [Tert-butoxycarbonyl-(4-morpholin-4-yl-phenyl)-amino]-propynoic acid methyl ester

HRID 623682Notes

Reaction equation

[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:11]([O:15][C:16](=[O:32])[N:17]([C:30]#[CH:31])[C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:20][CH:19]=1)([CH3:14])([CH3:13])[CH3:12].Cl[C:34]([O:36][CH3:37])=[O:35].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[CH3:37][O:36][C:34](=[O:35])[C:31]#[C:30][N:17]([C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:32])[C:18]1[CH:19]=[CH:20][C:21]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)=[CH:22][CH:23]=1

Participants

Conditions

Temperature: -40 °C

Procedure

LiHMDS (4.35 ml, 1 M in THF, 4.35 mmol) was added to a solution of ethynyl-(4-morpholin-4-yl-phenyl)-carbamic acid tert-butyl ester (750 mg, 2.5 mmol, in dry THF (4.3 ml) under nitrogen at −78° C. The mixture was slowly warmed up to −40° C. and maintained at this temperature for 1 hour. The latter was then transferred dropwise via cannula to a solution of ClCO2Me (314 μl, 4.06 mmol) in THF (7.5 ml) at −40° C. The resulting mixture was allowed to return to RT. Saturated aqueous NH4Cl and AcOEt were added and the organic phase was extracted (3×15 ml AcOEt) and dried over Na2SO4. The title compound was obtained after purification by column chromatography (PE/AcOEt:80/20 to 75/25).

Workup

customat −78° C
temperaturemaintained at this temperature for 1 hour
customto return to RT
extractionthe organic phase was extracted (3×15 ml AcOEt)
dry with materialdried over Na2SO4

Sources & evidence

ORD record: ord-6d6f44f9ac9543cc97559193db559731
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09302998B2

Reaction notes

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