Formaldehyde → HCID 67270741, compound

HRID 1039705Notes

Reaction equation

HRID 1039705 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:9][C@H:10]([NH:33][C:34](=[O:36])[CH3:35])[C@H:11]([OH:32])[CH2:12][NH:13][C@@H:14]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([CH2:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH:22]=3)[O:17][C:16]3([CH2:31][CH2:30][CH2:29]3)[CH2:15]2)[CH:5]=[CH:6][C:7]=1[F:8].[CH:37](OC)(OC)OC.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH2:9][C@H:10]([NH:33][C:34](=[O:36])[CH3:35])[C@H:11]([OH:32])[CH2:12][N:13]([C@@H:14]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([CH2:24][C:25]([CH3:27])([CH3:28])[CH3:26])[CH:22]=3)[O:17][C:16]3([CH2:31][CH2:30][CH2:29]3)[CH2:15]2)[CH3:37])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 9005Trimethyl orthoformateHCID 5049666Sodium triacetoxyborohydrideHCID 57950902HCID 57950902, compound

Product 1

HCID 67270741HCID 67270741, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 15-mL RB flask, N-((1S,2R)-1-((3-bromo-4-fluorophenyl)methyl)-3-(((4′S)-6′-(2,2-dimethylpropyl)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-b]pyridin]-4′-yl)amino)-2-hydroxypropyl)acetamide (0.027 g, 0.048 mmol) was dissolved in DCM (1.5 mL). Trimethyl orthoformate (0.13 ml, 1.2 mmol) was added, followed by addition of Formaldehyde (37%, 0.0089 ml, 0.12 mmol) as an aqueous solution. The mixture was stirred at ambient temperature for 2 h. Then sodium triacetoxyborohydride (0.036 g, 0.17 mmol) was added, and the mixture was stirred at ambient temperature overnight. The reaction mixture was quenched with 10% aqueous sodium carbonate (5 mL), stirred vigorously for 2 h, and diluted with DCM (60 mL). The organic layer was separated and extracted with dilute brine (5 mL), dried over sodium sulfate and concentrated. The residue was purified by passing it through silica gel (20 g; deactivated with triethylamine (2.0 mL)), eluting with 95% EtOAc-hexane to provide the title compound. MS m/z 576/578 (M+1).

Workup

  1. stirringthe mixture was stirred at ambient temperature overnight
  2. customThe reaction mixture was quenched with 10% aqueous sodium carbonate (5 mL)
  3. stirringstirred vigorously for 2 h
  4. additiondiluted with DCM (60 mL)
  5. customThe organic layer was separated
  6. extractionextracted with dilute brine (5 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified
  10. washeluting with 95% EtOAc-hexane

Sources & evidence

ORD record
ord-dff0b5f7bf2949b5abcb1989836adada
Source dataset
uspto-grants-2013_10
Patent number
US08552181B2

Reaction notes

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