3,3-Dimethylbutanal → cis-2-(3,3-Dimethyl-butylamino)-cycloheptanecarboxylic acid methyl ester

HRID 731328Notes

Reaction equation

HRID 731328 reaction equation
C([O-])(=O)C.[Na+].[CH3:6][C:7]([CH3:12])([CH3:11])[CH2:8][CH:9]=O.C([BH3-])#N.[Na+].Cl.[CH3:18][O:19][C:20]([C@@H:22]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]1[NH2:29])=[O:21]>CO>[CH3:18][O:19][C:20]([C@@H:22]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]1[NH:29][CH2:9][CH2:8][C:7]([CH3:12])([CH3:11])[CH3:6])=[O:21]

Participants

6

Reactant 4

HCID 763353,3-DimethylbutanalHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 66658076rac-methyl (1R,2S)-2-aminocycloheptane-1-carboxylate hydrochloride

Product 1

HCID 69069150cis-2-(3,3-Dimethyl-butylamino)-cycloheptanecarboxylic acid methyl esterYield 29.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

Sodium acetate (0.197 g, 2.40 mmol), powdered 4 Å molecular sieves (0.60 g), 3,3-dimethylbutyraldehyde (0.151 mL, 1.20 mmol) and sodium cyanoborohydride (0.151 mg, 2.40 mmol) were added sequentially to a solution of cis-2-amino-cycloheptanecarboxylic acid methyl ester hydrochloride (prepared as described in Example 2a, 0.250 g, 1.20 mmol) in methanol (10 mL) at 25° C. The reaction mixture was stirred at 25° C. for 3 h, and then was partitioned between half-saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (2×150 mL). The organic layers were washed sequentially with half-saturated aqueous sodium bicarbonate solution (100 mL) and saturated aqueous brine solution (100 mL), then were dried over sodium sulfate, filtered, and were concentrated in vacuo. The residue was purified by flash column chromatography (Analogix SuperFlash Column; 0-25% ethyl acetate in hexanes) to afford the desired product, cis-2-(3,3-dimethyl-butylamino)-cycloheptanecarboxylic acid methyl ester (0.090 g, 0.352 mmol, 29%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.90 (s, 9H), 1.33-1.37 (m, 2H), 1.43-1.50 (m, 3H), 1.58-1.87 (m, 7H), 2.46-2.53 (m, 1H), 2.58-2.65 (m, 1H), 2.81-2.85 (m, 1H), 2.95-2.99 (m, 1H), 3.67 (s, 3H). LC-MS (ESI) calcd for C15H29NO2 255.22, found 256.3 [M+H+].

Workup

  1. customwas partitioned between half-saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (2×150 mL)
  2. washThe organic layers were washed sequentially with half-saturated aqueous sodium bicarbonate solution (100 mL) and saturated aqueous brine solution (100 mL)
  3. dry with materialwere dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationwere concentrated in vacuo
  6. customThe residue was purified by flash column chromatography (Analogix SuperFlash Column; 0-25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e136a39a41bf4f2dab942eac20531b47
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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