Dichloromethane → 4-benzyl-2-(S)-(3,5-dichlorobenzyloxy)-3-(S)-phenylmorpholine

HRID 1004095Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][C:10](=[O:14])[C@@H:9]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([BH-](C(CC)C)C(CC)C)(CC)C.[Li+].[Cl:35][C:36]1[CH:37]=[C:38]([CH:41]=[C:42]([Cl:44])[CH:43]=1)[CH2:39]O.C(Cl)Cl>C1COCC1.C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([O:14][CH2:39][C:38]2[CH:37]=[C:36]([Cl:35])[CH:43]=[C:42]([Cl:44])[CH:41]=2)[C@@H:9]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -75 °C

Procedure

A solution of 5.11 g (19.1 mmole) of N-benzyl-3-(S)-phenylmorpholine-2-one (from Example 14) in 100 mL of dry THF was cooled to -75° C. under nitrogen and was treated dropwise with 20.5 mL (20.5 mmole) of a 1M solution of lithium tri(sec-butyl)borohydride (L-Selectride®) in THF. After stirring the solution at -75° C. for 30 min, a solution of 3,5-dichlorobenzyl alcohol, trifluoromethanesulfonate ester in toluene (from Example 44, Step A) was added by cannula so that the on 67 g of silica eluting with 1.5 L of 100:1 methylene chloride: methanol, and the rich cuts were purified by flash chormatography on 32 g of silica eluting with 50:50 hexanes: ethyl acetate and then 50:50:5 hexanes:ethyl acetate:methanol to give 0.051 g (20%) of an oil, which by 1H NMR was pure cis morpholine.

Workup

custommethanol, and the rich cuts were purified by flash chormatography on 32 g of silica eluting with 50:50 hexanes

Sources & evidence

ORD record: ord-8536ec3cf4ae472ba9cddc843d0cece6
Source dataset: uspto-grants-2000_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06048859

Reaction notes

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