Sodium Bicarbonate → HCID 71227009, compound

HRID 2359384Notes

Reaction equation

HRID 2359384 reaction equation
Cl.[O:2]1[C:6]2([CH2:10][CH2:9][NH:8][CH2:7]2)[CH2:5][CH2:4][CH2:3]1.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[O:23][C:22]([C:24]([N:26]3[CH2:29][CH:28]([O:30][C:31]4[CH:38]=[CH:37][C:34]([CH:35]=O)=[CH:33][CH:32]=4)[CH2:27]3)=[O:25])=[N:21][N:20]=2)=[CH:15][CH:14]=1.[Na].C([O-])(O)=O.[Na+]>C(Cl)Cl>[O:2]1[C:6]2([CH2:10][CH2:9][N:8]([CH2:35][C:34]3[CH:33]=[CH:32][C:31]([O:30][CH:28]4[CH2:29][N:26]([C:24]([C:22]5[O:23][C:19]([C:16]6[CH:17]=[CH:18][C:13]([O:12][CH3:11])=[CH:14][CH:15]=6)=[N:20][N:21]=5)=[O:25])[CH2:27]4)=[CH:38][CH:37]=3)[CH2:7]2)[CH2:5][CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 580430894-(1-(5-(4-Methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehydeHCID 86690185HCID 86690185, compound

Product 1

HCID 71227009HCID 71227009, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-oxa-7-azaspiro[4.4]nonane hydrochloride (65 mg, 0.40 mmol) and TEA (0.082 mL, 0.59 mmol) were mixed with DCM (4 mL). To the mixture was added 4-(1-(5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.150 g, 0.40 mmol) dissolved in DCM (1 mL). After stirring for 10 min, sodium triacetoxyhydroborate (0.168 g, 0.79 mmol) was added and the reaction mixture was stirred at RT overnight. An aqueous solution of NaHCO3 (8%, 10 mL) was added and the mixture was extracted twice with DCM (15 mL). The organic layer was dried over a phase separator and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (25 g) eluting with a mixture of EtOAc and ammonia in MeOH (2M) 20:1. The pooled fractions were concentrated under reduced pressure yielding the desired compound as a white solid (95 mg, 49%). 1H NMR (400 MHz, CDCl3): δ 1.73 (m, 5H), 1.86 (m, 1H), 2.57 (m, 3H), 2.69 (m, 1H), 3.56 (m, 2H), 3.77 (m, 2H), 3.88 (s, 3H), 4.32 (dd, 1H), 4.63 (m, 1H), 4.73 (dd, 1H), 5.07 (m, 2H), 6.71 (d, 2H), 7.01 (d, 2H), 7.27 (d, 2H), 8.09 (d, 2H). MS (APCI+) m/z 491.5 [M+H]+. LC purity: 94%.

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. extractionthe mixture was extracted twice with DCM (15 mL)
  3. customThe organic layer was dried over a phase separator
  4. concentrationconcentrated under reduced pressure
  5. customThe crude was purified by chromatography on silica gel (25 g)
  6. washeluting with a mixture of EtOAc and ammonia in MeOH (2M) 20:1
  7. concentrationThe pooled fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-d7300ff82bff4c1dba32a6ea7fc260cd
Source dataset
uspto-grants-2014_04
Patent number
US08685958B2

Reaction notes

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