Cyclobutanone → HCID 46855230, compound

HRID 882766Notes

Reaction equation

HRID 882766 reaction equation
[C:1]1(=O)[CH2:4][CH2:3][CH2:2]1.[N:6]1([C:13]([C@H:15]2[CH2:19][C@@H:18]([OH:20])[CH2:17][N:16]2[C:21](=[O:23])[CH3:22])=[O:14])[CH2:12][CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].[O-]S([O-])(=O)=O.[Mg+2]>ClC(Cl)C>[CH:1]1([N:9]2[CH2:10][CH2:11][CH2:12][N:6]([C:13]([C@H:15]3[CH2:19][C@@H:18]([OH:20])[CH2:17][N:16]3[C:21](=[O:23])[CH3:22])=[O:14])[CH2:7][CH2:8]2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 14496CyclobutanoneHCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 5049666Sodium triacetoxyborohydrideHCID 46855231HCID 46855231, compound

Product 1

HCID 46855230HCID 46855230, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of cyclobutanone (137 mL, 1.83 mol) and (2R,4R)1-[2-([1,4]diazepane-1-carbonyl)-4-hydroxy-pyrrolidin-1-yl]-ethanone (358 g, 1.4 mol) in dichloroethane (3.7 L) was stirred for 1 h at rt. Sodium triacetoxyborohydride (422.4 g, 1.99 mol) was then added in 4 portions over 2 h. The mixture was stirred for 14 h and then NaOH(aq) (50 wt %, 210 mL) was added. The mixture was stirred for 2 h and then MgSO4 (264 g) was added. After an additional 1.5 h of stirring, the mixture was filtered and then concentrated. Purification by FCC (5% 2 M NH3 in MeOH/95% CH2Cl2) provided the title compound as an oil (277 g, 64%). MS (ESI): mass calcd. for C16H27N3O3, 309.2; m/z found, 310.2 [M+H]+. 1H NMR (CDCl3): 6.11-6.04 (m, 1H), 4.93-4.70 (m, 1H), 4.46-4.34 (m, 1H), 3.96-3.44 (m, 6H), 2.96-2.83 (m, 1H), 2.76-2.37 (m, 4H), 2.30-2.20 (m 1H), 2.10-1.55 (m, 12H).

Workup

  1. stirringThe mixture was stirred for 2 h
  2. stirringAfter an additional 1.5 h of stirring
  3. filtrationthe mixture was filtered
  4. concentrationconcentrated
  5. customPurification by FCC (5% 2 M NH3 in MeOH/95% CH2Cl2)

Sources & evidence

ORD record
ord-f48bf6de07104c32a109453731a1d8ad
Source dataset
uspto-grants-2012_08
Patent number
US08236792B2

Reaction notes

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