4-Methylmorpholine → Phenylmethyl 1-[[[(1-chloroethoxy)carbonyl]amino]methyl]cyclohexaneacetate

HRID 30513Notes

Reaction equation

Cl.[NH2:2][CH2:3][C:4]1([CH2:10][C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.Cl[C:22]([O:24][CH:25]([Cl:27])[CH3:26])=[O:23].CN1CCOCC1>ClCCl>[Cl:27][CH:25]([O:24][C:22]([NH:2][CH2:3][C:4]1([CH2:10][C:11]([O:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1)=[O:23])[CH3:26]

Participants

Conditions

Temperature: 15 °C

Procedure

In a 5-liter, 3-neck, round bottom flask, stirred mechanically and under nitrogen, was added dichloromethane (1.5 L), compound (6) (1.85 mol) and 1-chloroethyl chloroformate (258 g, 1.81 mol). The resulting solution was cooled to 15° C. and N-methylmorpholine (396 mL, 3.60 mol) was added slowly, with cooling, over a one hour period. The resulting turbid solution was stirred for 30 min, after which 1H—NMR analysis showed the reaction to be complete. The reaction mixture was washed with water (2×2 L) and brine (1 L) and dried over sodium sulfate. Evaporation of the solvent afforded the title compound (9) as an orange oil (670 g, 98% yield). 1HNMR (CDCl3, 400 MHz): 1.33-1.53 (m, 10H), 1.75 (d, 3H), 2.33 (s, 2H), 3.18 (d, 2H), 5.09 (s, 2H), 5.58 (t, 1H), 6.53 (q, 1H), 7.29-7.33 (m, 5H).

Workup

temperaturewith cooling, over a one hour period
stirringThe resulting turbid solution was stirred for 30 min
customthe reaction
washThe reaction mixture was washed with water (2×2 L) and brine (1 L)
dry with materialdried over sodium sulfate
customEvaporation of the solvent

Sources & evidence

ORD record: ord-3ae72ad6912c42f2a5832eeb826534d7
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07423169B2

Reaction notes

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