Isobutyraldehyde → (1-Carbamoylmethyl-cyclohexylmethyl)-carbamic Acid tert-butyl Ester

HRID 1058929Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1([CH2:16][C:17]([OH:19])=O)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:22](CC)CC)C.C(=O)C(C)C>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10]1([CH2:16][C:17](=[O:19])[NH2:22])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

[1-(tert-Butoxycarbonylamino-methyl)-cyclohexyl]-acetic acid (2) (152 g, 0.56 mdl) was taken up in 1 L THF and triethylamine (66.2 g, 0.65 mol) and cooled to −10° C. Over a 1-hour period, isobutyraldehyde was added (84.7 g, 0.62 mol), and the heterogeneous mixture was stirred at 0° C. for 15 minutes. Ammonia gas was bubbled into the cold reaction mixture for 30 minutes, and the mixture was allowed to warm to room temperature. After 16 hours stirring, the reaction mixture was evaporated to dryness on a rotary evaporator, and the residue was taken up in water, extracted 3× EtOAc, washed 2× brine and dried over MgSO4. Evaporation yielded an oil which was crystallized from pentane to yield 116.5 g (77%) white crystals, mp 123-125° C.

Workup

customAmmonia gas was bubbled into the cold reaction mixture for 30 minutes
temperatureto warm to room temperature
stirringAfter 16 hours stirring
customthe reaction mixture was evaporated to dryness on a rotary evaporator
extractionextracted 3× EtOAc
washwashed 2× brine
dry with materialdried over MgSO4
customEvaporation
customyielded an oil which
customwas crystallized from pentane

Sources & evidence

ORD record: ord-7b3a5e90d6d6484aa9cfd8884186fc57
Source dataset: uspto-grants-2003_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06518289B1

Reaction notes

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