Borane;pyridine → 4-[3-((-)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 1867395Notes

Reaction equation

HRID 1867395 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]([CH2:16][CH2:17][CH:18]=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:21]1[C:23]2([CH2:28][CH2:27][NH:26][CH2:25][CH:24]2[OH:29])[CH2:22]1.B.N1C=CC=CC=1>ClCCCl.CCO.CC(O)=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]([CH2:16][CH2:17][CH2:18][N:26]2[CH2:27][CH2:28][C:23]3([CH2:21][CH2:22]3)[CH:24]([OH:29])[CH2:25]2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 2723995Borane;pyridineHCID 667835826-Azaspiro[2.5]octan-4-OL hydrochloride2×HCID 866158685-Oxo-4-(3-oxo-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester2×

Product 1

HCID 684402844-[3-((-)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl esterYield 93.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 229016121,2-Dichloroethane ethanolSolvent

Procedure

5-Oxo-4-(3-oxo-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (intermediate 61) (0.19 g, 0.7 mmol) was reacted with (−)-6-Aza-spiro[2.5]octan-4-ol hydrochloride (intermediate 83) (0.12 g, 0.7 mmol) in DCE:EtOH (1:1, 6 ml), AcOH (0.18 ml) and pyridine-borane complex (0.18 ml, 8M in pyridine, 1.4 mmol) for 20 minutes. The reaction was then concentrated, redissolved in CH2Cl2 and washed with sat. NaHCO3, dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (CH2Cl2:MeOH 8:2) to afford the title product (0.25 g, 91%) as a gum. MS: 382.4 (MH+).

Workup

  1. concentrationThe reaction was then concentrated
  2. dissolutionredissolved in CH2Cl2
  3. washwashed with sat. NaHCO3
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography (CH2Cl2:MeOH 8:2)

Sources & evidence

ORD record
ord-fab9f11bec2245bc84c52135b74d683b
Source dataset
uspto-grants-2009_12
Patent number
US07632829B2

Reaction notes

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