Trimethyl orthoformate → HCID 59129101, compound

HRID 2390499Notes

Reaction equation

HRID 2390499 reaction equation
[CH2:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[C:11]([OH:12])[C:6]=2[CH2:5][CH2:4][NH:3][CH2:2]1.[CH3:13][C:14]([CH3:18])([CH3:17])[CH:15]=O.C(OC)(OC)OC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1CCCC1=O.C(O)(=O)C>[CH2:13]([N:3]1[CH2:4][CH2:5][C:6]2[C:11]([OH:12])=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:1][CH2:2]1)[C:14]([CH3:18])([CH3:17])[CH3:15]

Participants

7

Reactant 4

HCID 9005Trimethyl orthoformateHCID 12417PivalaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 13338341HCID 13338341, compound

Product 1

HCID 59129101HCID 59129101, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 2,3,4,5-tetrahydro-1H-benzo[d]azepin-6-ol (see Demarinis et al. J. Med. Chem. 1984, 27, 918-921) (60 mg, 0.37 mmol), trimethylacetaldehyde (400 μL, 3.7 mmol), trimethyl orthoformate (390 μL, 3.7 mmol) and glacial acetic acid (40 μL) in 1-methyl-2-pyrrolidinone (2.5 mL) was stirred at rt for 2.5 h. Sodium triacetoxyborohydride (388 mg, 1.8 mmol) was then added and the mixture was stirred at room temperature for 16 h. The mixture was then loaded on top of a silica gel-SCX (sulfonic acid) column and eluted first with methanol, then with 2 M ammonia in methanol. The latter fraction was evaporated and the resulting 3-neopentyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-6-ol was used in the next step without further purification. (M+H)+=234.0.

Workup

  1. stirringthe mixture was stirred at room temperature for 16 h
  2. washeluted first with methanol
  3. customThe latter fraction was evaporated
  4. customthe resulting 3-neopentyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-6-ol was used in the next step without further purification

Sources & evidence

ORD record
ord-1cdebf125cf7474c9e6b25ef859476ff
Source dataset
uspto-grants-2012_09
Patent number
US08273772B2

Reaction notes

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