Ammonia → (1R,3S)-3-(Boc-amino)cyclohexanecarboxamide

HRID 1257715Notes

Reaction equation

HRID 1257715 reaction equation
C(OC(Cl)=O)C(C)C.[C:9]([O:13][C:14]([NH:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH:19]([C:23]([OH:25])=O)[CH2:18]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C[N:27]1CCOCC1.N>C1COCC1>[C:9]([O:13][C:14](=[O:15])[NH:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH:19]([C:23](=[O:25])[NH2:27])[CH2:18]1)([CH3:12])([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 44203163-(((Tert-butoxy)carbonyl)amino)cyclohexane-1-carboxylic acid

Product 1

HCID 67324654(1R,3S)-3-(Boc-amino)cyclohexanecarboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Isobutylchloroformate (2.06 g, 15.0 mmol) was added dropwise with cooling in an ice-methanol bath to a solution of 3-tert-butoxycarbonylamino-cyclohexanecarboxylic acid (3.15 g, 13.0 mmol) and N-methylmorpholine (1.52 g, 15.0 mmol) in THF (40 mL). After stirring for 30 mins, methanolic ammonia (7M, 5 mL) was added. The mixture was allowed to warm to room temperature, and left to stand overnight. The residue remaining on evaporation of solvent was partitioned between aq. NH4Cl (150 mL) and DCM (150 mL). The solid suspended in the organic layer was collected, the filtrate evaporated, and the combined solids crystallised from methanol to afford 2.07 (66%) of (3-carbamoyl-cyclohexyl)-carbamic acid tert-butyl ester as colourless plates. 1H NMR (400 MHz, MeOD) δ: 6.65-6.59 (m, 1H), 3.40-3.28 (m, 1H), 2.35-2.23, (m, 1H), 2.01-1.92 (m, 1H), 1.91-1.80 (m, 2H), 1.80-1.71 (m, 1H), 1.42 (s, 9H), 1.40-1.21 (m, 3H), 1.19-1.05 (m, 1H).

Workup

  1. waitleft
  2. waitto stand overnight
  3. customThe residue remaining on evaporation of solvent
  4. customwas partitioned between aq. NH4Cl (150 mL) and DCM (150 mL)
  5. customwas collected
  6. customthe filtrate evaporated
  7. customthe combined solids crystallised from methanol

Sources & evidence

ORD record
ord-3e47cc688fb7499eb2fdfec9c1c73b7f
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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