3-azetidinecarboxylic Acid → HCID 67170299, compound

HRID 1506384Notes

Reaction equation

HRID 1506384 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:14][CH2:15][C:16]3[O:17][C:18]4[CH:28]=[CH:27][C:26]5[C:21](=[CH:22][CH:23]=[C:24]([CH:29]=O)[CH:25]=5)[C:19]=4[N:20]=3)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH:31]1[CH2:34][CH:33]([C:35]([OH:37])=[O:36])[CH2:32]1.C([BH3-])#N.[Na+].CO.ClCCl>ClC(Cl)C.CO.C(O)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:14][CH2:15][C:16]3[O:17][C:18]4[CH:28]=[CH:27][C:26]5[C:21](=[CH:22][CH:23]=[C:24]([CH2:29][N:31]6[CH2:34][CH:33]([C:35]([OH:37])=[O:36])[CH2:32]6)[CH:25]=5)[C:19]=4[N:20]=3)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 21226129Dichloromethane methanolHCID 86669890HCID 86669890, compound

Product 1

HCID 67170299HCID 67170299, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(2-(1-(4-fluorophenyl)cyclohexyl)ethyl)naphtho[1,2-d]oxazole-7-carbaldehyde (Preparation 42E, 47.0 mg, 0.117 mmol) in dichloroethane (1 mL) and methanol (1 mL) was added azetidine-3-carboxylic acid (23.66 mg, 0.234 mmol) followed by 2 drops of acetic acid. Next, the reaction mixture was stirred in a 60° C. in an oil bath for 1 hr. After cooling to room temp sodium cyanoborohydride (14.71 mg, 0.234 mmol) was added, and the mixture was stirred at room temperature overnight. Next, the reaction mixture was placed on a Combiflash column (12 g silica gel) filled with 7:93 methanol-dichloromethane, and eluted with 2:8 followed by 3:7 and 1:1 MeOH—CH2Cl2 to give the 1-((2-(2-(1-(4-fluorophenyl)cyclohexyl)ethyl)naphtho[1,2-d]oxazol-7-yl)methyl)azetidine-3-carboxylic acid as a brown solid. LC/MS M+1=487.31; 1H NMR (400 MHz, CDCl3) δ ppm 8.31 (1H, d, J=8.36 Hz), 7.81 (1H, s), 7.58 (1H, d, J=9.02 Hz), 7.50 (1H, d, J=8.80 Hz), 7.46 (1H, d, J=9.02 Hz), 7.24-7.31 (2H, m), 6.98 (2H, t, J=8.69 Hz), 4.03 (2H, br. s.), 3.79-3.96 (4H, m), 3.31 (1H, br. s.), 2.51-2.60 (2H, m), 2.00-2.14 (4H, m), 1.29-1.65 (8H, m).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature overnight
  3. washeluted with 2:8

Sources & evidence

ORD record
ord-dead8cf567134850b9c00c12d0e499eb
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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