Acetic Acid → 3-[10-bromo-2-(trifluoromethyl)-5,6,8,9-tetrahydro-7H-[1,3]oxazolo[4,5-h][3]benzazepin-7-yl]-1-butanol

HRID 1668594Notes

Reaction equation

HRID 1668594 reaction equation
[Br:1][C:2]1[C:12]2[CH2:11][CH2:10][NH:9][CH2:8][CH2:7][C:6]=2[CH:5]=[C:4]2[N:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[O:15][C:3]=12.[OH:20][CH2:21][CH2:22][C:23](=O)[CH3:24].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[C:12]2[CH2:11][CH2:10][N:9]([CH:23]([CH3:24])[CH2:22][CH2:21][OH:20])[CH2:8][CH2:7][C:6]=2[CH:5]=[C:4]2[N:13]=[C:14]([C:16]([F:19])([F:17])[F:18])[O:15][C:3]=12

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 1115094-Hydroxy-2-Butanone2×HCID 5049666Sodium triacetoxyborohydride2×HCID 5915052210-bromo-2-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-[1,3]oxazolo[4,5-h][3]benzazepine

Product 1

HCID 591504983-[10-bromo-2-(trifluoromethyl)-5,6,8,9-tetrahydro-7H-[1,3]oxazolo[4,5-h][3]benzazepin-7-yl]-1-butanolYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 10-bromo-2-(trifluoromethyl)-6,7,8,9-tetrahydro-5H-[1,3]oxazolo[4,5-h][3]benzazepine (250 mg, 1 eq), 4-hydroxy-butan-2-one (0.077 ml, 1.2 eq), acetic acid (0.042 ml, 1 eq) and sodium triacetoxyborohydride (314 mg, 2 eq) in THF (2.5 ml) was stirred at room temperature for 20 hours. Additional 4-hydroxy-butan-2-one (0.24 eq) and sodium triacetoxyborohydride (0.4 eq) were added and the mixture was stirred for 5 hours. Then, the mixture was diluted with DCM and washed with 5% NaHCO3 and brine. The organic phase was dried (Na2SO4) and concentrated. The crude was purified on silica gel (DCM/MeOH/conc.NH4OH, 100/2.5/0.25) providing the title compound (218 mg, 72% yield).

Workup

  1. stirringthe mixture was stirred for 5 hours
  2. washwashed with 5% NaHCO3 and brine
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude was purified on silica gel (DCM/MeOH/conc.NH4OH, 100/2.5/0.25)

Sources & evidence

ORD record
ord-6cbb3b33be2640de97d8941e8d25c7f1
Source dataset
uspto-grants-2011_08
Patent number
US07989444B2

Reaction notes

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