Tetrahydro-4H-pyran-4-one → [(R)-1-phenyl-2-(tetrahydro-pyran-4-ylamino)-ethyl]-carbamic acid tert-butyl ester

HRID 1711188Notes

Reaction equation

HRID 1711188 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:9][NH2:10])([CH3:4])([CH3:3])[CH3:2].[O:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH2:9][NH:10][CH:21]1[CH2:22][CH2:23][O:18][CH2:19][CH2:20]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 15675183[(1R)-2-AMINO-1-PHENYLETHYL]-CARBAMIC ACID 1,1-DIMETHYLETHYL ESTER

Product 1

HCID 68777024[(R)-1-phenyl-2-(tetrahydro-pyran-4-ylamino)-ethyl]-carbamic acid tert-butyl esterYield 91.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Following general procedure A: ((R)-2-amino-1-phenyl-ethyl)-carbamic acid tert-butyl ester (269 mg, 1.14 mmol), tetrahydro-4H-pyran-4-one (0.12 ml, 1.3 mmol) and NaBH(OAc)3 (340 mg, 1.60 mmol) in CH2Cl2 (8.0 ml) was stirred at room temperature for 18 hours. Standard work-up and purification by flash column chromatography on silica (CH2Cl2/MeOH, 19:1) gave [(R)-1-phenyl-2-(tetrahydro-pyran-4-ylamino)-ethyl]-carbamic acid tert-butyl ester as a colorless oil (333 mg, 91%). 1H NMR (CDCl3) δ 0.80-1.36 (m, 3H), 1.41 (s, 9H), 1.68-1.82 (m, 2H), 2.61 (tt, 1H, J=10.3, 4.1 Hz), 2.93 (d, 2H, J=5.1 Hz), 3.35 (tdd, 2H, J=11.6, 5.6, 2.2 Hz), 3.88-3.96 (m, 2H), 4.74 (br s, 1H), 5.45 (br d, 1H, J=5.7 Hz), 7.22-7.35 (m, 5H).

Workup

  1. customStandard work-up and purification by flash column chromatography on silica (CH2Cl2/MeOH, 19:1)

Sources & evidence

ORD record
ord-7c8eb84a18c942618450e7d84452d58c
Source dataset
uspto-grants-2010_09
Patent number
US07790747B2

Reaction notes

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