Ammonia → HCID 22270608, compound

HRID 30375Notes

Reaction equation

HRID 30375 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][CH:7]([C:18](=O)[CH3:19])[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])=[CH:4][CH:3]=1.N.C([BH3-])#[N:25].[Na+].C(Cl)Cl>CO.C(O)(=O)C>[NH2:25][CH:18]([CH3:19])[CH:7]([CH2:6][C:5]1[CH:21]=[CH:22][C:2]([Cl:1])=[CH:3][CH:4]=1)[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6344DichloromethaneHCID 5003444Sodium cyanoborohydrideHCID 22270747HCID 22270747, compound

Product 1

HCID 22270608HCID 22270608, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

Benzyl 2-(4-chlorobenzyl)-3-ketobutyrate (317 mg, 1 mmole, obtained from Step A) was added to a cooled mixture of 7M ammonia in MeOH (2.42 mL) and glacial acetic acid (1.6 mL). To this solution, at ˜10° C., was added sodium cyanoborohydride (101 mg, 1.75 mmol) in small portions. This mixture was stirred at room temperature for 40 h. The excess sodium cyanoborohydride was destroyed by the addition of 6M HCl (to pH 1). The residue obtained after removal of volatiles was taken up in a minimal amount of water and extracted with ether. The aqueous layer was basified to pH 10 using solid KOH. This layer was then saturated with sodium chloride and then extracted with EtOAc. Further analyses of the ether and the EtOAc layers suggest that the desired product resides the EtOAc layer. This material was used in the ensuing coupling reaction without further purification. Proton NMR spectrum show that the two pairs of diastereomers are obtained in ˜1:1 ratio, homogeneous by TLC, Rf=0.4 in 95:5 CH2Cl2:MeOH. LC/MS m/e=318 (M+1). 400 MHz 1H NMR (CDCl3) δ 1.27, 1.29 (2 d, J=7Hz, 3H), 2.85 (m, 1H), 3.03 (m, 1H), 3.15 (m, 1H), 3.55 (m, 1H), 4.85 (br, 2H), 5.00-5.18 (m, 2H), 7.0-7.2 (m, 9H).

Workup

  1. customThe excess sodium cyanoborohydride was destroyed by the addition of 6M HCl (to pH 1)
  2. customThe residue obtained
  3. customafter removal of volatiles
  4. extractionextracted with ether
  5. extractionsaturated with sodium chloride and then extracted with EtOAc
  6. customThis material was used in the ensuing coupling reaction without further purification

Sources & evidence

ORD record
ord-7e3fa5738d284e11b67a5010c6488848
Source dataset
uspto-grants-2008_09
Patent number
US07423067B2

Reaction notes

Loading…